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Del Castillo Falconi VM, Godinez Rodriguez JA, Fragoso-Ontiveros V, Contreras-Espinosa L, Pedroza-Torres A, Díaz-Chávez J, Herrera LA. Role of DNA methylation and non‑coding RNAs expression in pathogenesis, detection, prognosis, and therapy‑resistant ovarian carcinoma (Review). Mol Med Rep 2025; 31:144. [PMID: 40183399 PMCID: PMC11979574 DOI: 10.3892/mmr.2025.13509] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2024] [Accepted: 12/17/2024] [Indexed: 04/05/2025] Open
Abstract
Ovarian cancer is the deadliest gynecological cancer globally, with epithelial ovarian cancer (EOC) comprising up to 90% of cases. A molecular characterization linking the histological subtypes with tumor grade in EOC has been suggested. Variations in genetic biomarkers such as BRCA1/2, MSH2, MLH1/6, BRIP1, and RAD51C/D have been studied in EOC. In addition, molecular characteristics, including DNA methylation and RNA transcription, are being explored as potential new biomarkers for the diagnosis and prognosis of this type of neoplasia. The present review focused on the role of DNA methylation and non‑coding RNA expression in the development of ovarian carcinomas and their association with diagnosis, prognosis, and the resistance of cancer cells to radiotherapy and chemotherapy. The present review considered the transition from the DNA structure to the RNA expression in ovarian carcinoma.
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Affiliation(s)
- Victor M. Del Castillo Falconi
- Carcinogenesis Laboratory, Biomedical Cancer Research Unit of Biomedicine - National Autonomous University of Mexico (UNAM), National Cancer Institute (INCan), Mexico City 14080, Mexico
| | | | - Verónica Fragoso-Ontiveros
- Carcinogenesis Laboratory, Biomedical Cancer Research Unit of Biomedicine - National Autonomous University of Mexico (UNAM), National Cancer Institute (INCan), Mexico City 14080, Mexico
| | - Laura Contreras-Espinosa
- Carcinogenesis Laboratory, Biomedical Cancer Research Unit of Biomedicine - National Autonomous University of Mexico (UNAM), National Cancer Institute (INCan), Mexico City 14080, Mexico
- Biological Sciences Postgrade, UNAM, Mexico City 04510, Mexico
| | - Abraham Pedroza-Torres
- Investigadores por México Program - SECIHTI, Hereditary Cancer Clinic, INCan, Mexico City 14080, Mexico
| | - José Díaz-Chávez
- Carcinogenesis Laboratory, Biomedical Cancer Research Unit of Biomedicine - National Autonomous University of Mexico (UNAM), National Cancer Institute (INCan), Mexico City 14080, Mexico
- School of Medicine and Health Sciences, Mexico-Monterrey Institute of Technology, Mexico City 14380, Mexico
| | - Luis A. Herrera
- Carcinogenesis Laboratory, Biomedical Cancer Research Unit of Biomedicine - National Autonomous University of Mexico (UNAM), National Cancer Institute (INCan), Mexico City 14080, Mexico
- School of Medicine and Health Sciences, Mexico-Monterrey Institute of Technology, Mexico City 14380, Mexico
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Chen S, Wen JT, Zhang S, Wang JL, Yuan J, Bao HJ, Chen X, Zhao Y. SNORD9 promotes ovarian cancer tumorigenesis via METTL3/IGF2BP2-mediated NFYA m6A modification and is a potential target for antisense oligonucleotide therapy. Life Sci 2025; 368:123527. [PMID: 40044032 DOI: 10.1016/j.lfs.2025.123527] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Revised: 02/17/2025] [Accepted: 03/01/2025] [Indexed: 03/15/2025]
Abstract
C/D box small nucleolar noncoding RNAs (snoRNAs) are known to bind and induce 2'-O-ribose methylation of RNAs, participate in cancer tumorigenesis and development. However, their involvement in regulating m6A modification remains unreported. Analysis of the TCGA database revealed that SNORD9 was an unfavorable prognostic factor for ovarian cancer. Besides, SNORD9 was elevated in ovarian cancer. The overexpression of SNORD9 induced ovarian cancer cell proliferation and migration in vitro and induce tumorigenicity in vivo, increased the m6A modification level by binding to m6A-methyltransferase METTL3 to affect NFYA m6A modification; besides, m6A-reader IGF2BP2 was 2'-O-methylated by SNORD9, thereby affect NFYA mRNA stability, upregulate NFYA and its downstream proteins CCND1, CDK4 and VEGFA, promote ovarian cancer tumorigenesis. ASO-mediated silencing of SNORD9 suppressed tumorigenicity both in vitro and in vivo, and effectively inhibited the growth of patient-derived organoids of ovarian cancer (OC-PDO). In conclusions, we demonstrated for the first time that SNORD9 induces NFYA m6A methylation by binding to m6A methylase METTL3; modifying IGF2BP2 mRNA by 2'-O-methylation and improve NFYA mRNA stability, thus promote the tumorigenesis of ovarian cancer. Targeting ASO to SNORD9 may have efficacy in the treatment of ovarian cancer.
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Affiliation(s)
- Shuo Chen
- Department of Obstetrics and Gynecology, Department of Gynecologic Oncology Research Office; Guangzhou Key Laboratory of Targeted Therapy for Gynecologic Oncology; Guangdong Provincial Key Laboratory of Major Obstetric Diseases; Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology; Guangdong-Hong Kong-Macao Greater Bay Area Higher Education Joint Laboratory of Maternal-Fetal Medicine; The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China
| | - Jing-Tao Wen
- Department of Obstetrics and Gynecology, Department of Gynecologic Oncology Research Office; Guangzhou Key Laboratory of Targeted Therapy for Gynecologic Oncology; Guangdong Provincial Key Laboratory of Major Obstetric Diseases; Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology; Guangdong-Hong Kong-Macao Greater Bay Area Higher Education Joint Laboratory of Maternal-Fetal Medicine; The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China
| | - Song Zhang
- Department of Thoracic Surgery, The First Hospital of China Medical University, Shenyang 110001, China
| | - Jie-Lin Wang
- Department of Obstetrics and Gynecology, Department of Gynecologic Oncology Research Office; Guangzhou Key Laboratory of Targeted Therapy for Gynecologic Oncology; Guangdong Provincial Key Laboratory of Major Obstetric Diseases; Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology; Guangdong-Hong Kong-Macao Greater Bay Area Higher Education Joint Laboratory of Maternal-Fetal Medicine; The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China
| | - Jing Yuan
- Department of Obstetrics and Gynecology, Department of Gynecologic Oncology Research Office; Guangzhou Key Laboratory of Targeted Therapy for Gynecologic Oncology; Guangdong Provincial Key Laboratory of Major Obstetric Diseases; Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology; Guangdong-Hong Kong-Macao Greater Bay Area Higher Education Joint Laboratory of Maternal-Fetal Medicine; The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China
| | - Hai-Juan Bao
- Department of Obstetrics and Gynecology, Department of Gynecologic Oncology Research Office; Guangzhou Key Laboratory of Targeted Therapy for Gynecologic Oncology; Guangdong Provincial Key Laboratory of Major Obstetric Diseases; Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology; Guangdong-Hong Kong-Macao Greater Bay Area Higher Education Joint Laboratory of Maternal-Fetal Medicine; The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China
| | - Xi Chen
- Department of Obstetrics and Gynecology, Department of Gynecologic Oncology Research Office; Guangzhou Key Laboratory of Targeted Therapy for Gynecologic Oncology; Guangdong Provincial Key Laboratory of Major Obstetric Diseases; Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology; Guangdong-Hong Kong-Macao Greater Bay Area Higher Education Joint Laboratory of Maternal-Fetal Medicine; The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China
| | - Yang Zhao
- Department of Obstetrics and Gynecology, Department of Gynecologic Oncology Research Office; Guangzhou Key Laboratory of Targeted Therapy for Gynecologic Oncology; Guangdong Provincial Key Laboratory of Major Obstetric Diseases; Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology; Guangdong-Hong Kong-Macao Greater Bay Area Higher Education Joint Laboratory of Maternal-Fetal Medicine; The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China; Cancer Hospital of China Medical University, Cancer Hospital of Dalian University of Technology, Liaoning Cancer Hospital & Institute, Shenyang 110042, China.
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3
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Wang Y, Wang S, He H, Bai Y, Liu Z, Sabihi SS. Mechanisms of apoptosis-related non-coding RNAs in ovarian cancer: a narrative review. Apoptosis 2025; 30:553-578. [PMID: 39833637 DOI: 10.1007/s10495-024-02074-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/27/2024] [Indexed: 01/22/2025]
Abstract
Ovarian cancer remains a major challenge in oncology due to its complex biology and late-stage diagnosis. Recent advances in molecular biology have highlighted the crucial role of non-coding RNAs (ncRNAs) in regulating apoptosis and cancer progression. NcRNAs, including microRNAs, long non-coding RNAs, and circular RNAs, have emerged as significant players in the molecular networks governing ovarian cancer. Despite these insights, the precise mechanisms by which ncRNAs influence ovarian cancer pathology are not fully understood. This complexity, combined with the heterogeneity of the disease and the development of treatment resistance, poses substantial obstacles to effective therapeutic development. Additionally, the lack of reliable early detection methods further complicates treatment strategies. This manuscript reviews the current state of research on ncRNAs in ovarian cancer, discusses the challenges in translating these findings into clinical applications, and outlines potential future directions. Emphasis is placed on the need for integrated approaches to unravel the intricate roles of ncRNAs, improve early detection, and develop personalized treatment strategies to address the diverse and evolving nature of ovarian cancer. While these findings provide valuable insights, it is crucial to recognize that many results are based on preclinical studies and require further validation to establish their clinical applicability.
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Affiliation(s)
- Yue Wang
- Department of Obstetrics and Gynecology, Tang Du Hospital, The Air Force Military Medical University, Xi'an, 710038, China
| | - Shirui Wang
- Department of Obstetrics and Gynecology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710038, China
| | - Haiyan He
- Department of Obstetrics and Gynecology, Tang Du Hospital, The Air Force Military Medical University, Xi'an, 710038, China
| | - Yingying Bai
- Department of Obstetrics and Gynecology, Tang Du Hospital, The Air Force Military Medical University, Xi'an, 710038, China
| | - Zhuo Liu
- Department of Obstetrics and Gynecology, Xi'an International Medical Center Hospital, Xi'an, 710038, China
| | - Sima-Sadat Sabihi
- Food Security Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
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Afroze N, Sundaram MK, Haque S, Hussain A. Long non-coding RNA involved in the carcinogenesis of human female cancer - a comprehensive review. Discov Oncol 2025; 16:122. [PMID: 39912983 PMCID: PMC11803034 DOI: 10.1007/s12672-025-01848-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2024] [Accepted: 01/22/2025] [Indexed: 02/07/2025] Open
Abstract
Recent years have seen an increase in our understanding of lncRNA and their role in various disease states. lncRNA molecules have been shown to contribute to carcinogenesis and influence the various cancer hallmarks and signalling pathways. It is pertinent to understand the specific contributions and mechanisms of action of these molecules in various cancers. This review provides an overview of the various lncRNA entities that influence and regulate the gynaecological cancers, namely, cervical, breast, ovarian and uterine cancers. The review curates a list of the key players and their effect on cellular processes. lncRNA molecules show immense potential to be used as diagnostic and prognostic indicators and in therapeutic strategies. Several phytochemicals, small molecules, RNA-based regulators, oligos and gene editing tools show promise as a therapeutic strategy. While this review highlights the promising developments in this field, it also underscores the necessity for further research to delineate the complex role of lncRNAs in cancer.
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Affiliation(s)
- Nazia Afroze
- School of Life Sciences, Manipal Academy of Higher Education, Dubai Campus, P.O. Box 345050, Dubai, United Arab Emirates
| | - Madhumitha K Sundaram
- School of Life Sciences, Manipal Academy of Higher Education, Dubai Campus, P.O. Box 345050, Dubai, United Arab Emirates
| | - Shafiul Haque
- Department of Nursing, College of Nursing and Health Sciences, Jazan University, Jazan, Saudi Arabia
- School of Medicine, Universidad Espiritu Santo, Samborondon, Ecuador
| | - Arif Hussain
- School of Life Sciences, Manipal Academy of Higher Education, Dubai Campus, P.O. Box 345050, Dubai, United Arab Emirates.
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Basu S, Nadhan R, Dhanasekaran DN. Long Non-Coding RNAs in Ovarian Cancer: Mechanistic Insights and Clinical Applications. Cancers (Basel) 2025; 17:472. [PMID: 39941838 PMCID: PMC11815776 DOI: 10.3390/cancers17030472] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2024] [Revised: 01/25/2025] [Accepted: 01/28/2025] [Indexed: 02/16/2025] Open
Abstract
Background/Objectives: Ovarian cancer is a leading cause of gynecological cancer mortality worldwide, often diagnosed at advanced stages due to vague symptoms and the lack of effective early detection methods. Long non-coding RNAs (lncRNAs) have emerged as key regulators in cancer biology, influencing cellular processes such as proliferation, apoptosis, and chemoresistance. This review explores the multifaceted roles of lncRNAs in ovarian cancer pathogenesis and their potential as biomarkers and therapeutic targets. Methods: A comprehensive literature review was conducted to analyze the structural and functional characteristics of lncRNAs and their contributions to ovarian cancer biology. This includes their regulatory mechanisms, interactions with signaling pathways, and implications for therapeutic resistance. Advanced bioinformatics and omics approaches were also evaluated for their potential in lncRNA research. Results: The review highlights the dual role of lncRNAs as oncogenes and tumor suppressors, modulating processes such as cell proliferation, invasion, and angiogenesis. Specific lncRNAs, such as HOTAIR and GAS5, demonstrate significant potential as diagnostic biomarkers and therapeutic targets. Emerging technologies, such as single-cell sequencing, provide valuable insights into the tumor microenvironment and the heterogeneity of lncRNA expression. Conclusions: LncRNAs hold transformative potential in advancing ovarian cancer diagnosis, prognosis, and treatment. Targeting lncRNAs or their associated pathways offers promising strategies to overcome therapy resistance and enhance personalized medicine. Continued research integrating omics and bioinformatics will be essential to unlock the full clinical potential of lncRNAs in ovarian cancer management.
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Affiliation(s)
- Sneha Basu
- Stephenson Cancer Center, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; (S.B.); (R.N.)
- Department of Pathology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
| | - Revathy Nadhan
- Stephenson Cancer Center, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; (S.B.); (R.N.)
| | - Danny N. Dhanasekaran
- Stephenson Cancer Center, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; (S.B.); (R.N.)
- Department of Pathology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
- Department of Cell Biology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
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6
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Sharma A, Chowdhury S, Mukherjee S, Chowdhury R. LncRNA HULC augments high glucose-associated pancreatic cancer progression and drug resistance by enhancing YAP activity and autophagy. Biol Cell 2024; 116:e2400034. [PMID: 38949568 DOI: 10.1111/boc.202400034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Revised: 05/14/2024] [Accepted: 05/28/2024] [Indexed: 07/02/2024]
Abstract
BACKGROUND INFORMATION One of the confounding factors in pancreatic cancer (PC) pathogenesis is hyperglycemia. The molecular mechanism by which high glucose (HG) influences PC severity is poorly understood. Our investigation delved into the impact of lncRNA highly upregulated in liver cancer (HULC) and its interaction with yes-associated protein (YAP) in regulating the fate of pancreatic ductal adenocarcinoma cells (PDAC) under HG-induced conditions. PDAC cells were cultured under normal or HG conditions. We thereafter measured the effect of HG on the viability of PDAC cells, their migration potential and drug resistance properties. The lncRNAs putatively dysregulated in PC and diabetes were shortlisted by bioinformatics analysis followed by wet lab validation of function. RESULTS HG led to enhanced proliferation and drug refractoriness in PDAC cells. HULC was identified as one of the major deregulated lncRNAs following bioinformatics analysis. HULC was found to regulate the expression of the potent transcriptional regulator - YAP through selective histone modifications at the YAP promoter. siRNA-mediated ablation of HULC resulted in a concurrent decrease in YAP transcriptional activity. Importantly, HULC and YAP were found to co-operatively regulate the cellular homeostatic process autophagy, thus inculcating drug resistance and proliferative potential in PDAC cells. Moreover, inhibition of autophagy or YAP led to a decrease in HULC levels, suggesting the existence of an inter-regulatory feedback loop. CONCLUSIONS We observed that HG triggers aggressive properties in PDAC cells. Mechanistically, up-regulation of lncRNA HULC resulted in activation of YAP and differential regulation of autophagy coupled to increased proliferation of PDAC cells. SIGNIFICANCE Inhibition of HULC and YAP may represent a novel therapeutic strategy for PDAC. Furthermore, this study portrays the intricate molecular interplay between HULC, YAP and autophagy in PDAC pathogenesis.
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MESH Headings
- Humans
- Adaptor Proteins, Signal Transducing/metabolism
- Adaptor Proteins, Signal Transducing/genetics
- Autophagy/drug effects
- Carcinoma, Pancreatic Ductal/genetics
- Carcinoma, Pancreatic Ductal/metabolism
- Carcinoma, Pancreatic Ductal/pathology
- Cell Line, Tumor
- Cell Movement
- Cell Proliferation
- Disease Progression
- Drug Resistance, Neoplasm
- Gene Expression Regulation, Neoplastic
- Glucose/metabolism
- Glucose/pharmacology
- Pancreatic Neoplasms/genetics
- Pancreatic Neoplasms/pathology
- Pancreatic Neoplasms/metabolism
- RNA, Long Noncoding/genetics
- RNA, Long Noncoding/metabolism
- Transcription Factors/metabolism
- Transcription Factors/genetics
- YAP-Signaling Proteins/metabolism
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Affiliation(s)
- Ankita Sharma
- Department of Biological Sciences, Birla Institute of Technology and Science (BITS), Pilani, Rajasthan, India
| | - Shibasish Chowdhury
- Department of Biological Sciences, Birla Institute of Technology and Science (BITS), Pilani, Rajasthan, India
| | - Sudeshna Mukherjee
- Department of Biological Sciences, Birla Institute of Technology and Science (BITS), Pilani, Rajasthan, India
| | - Rajdeep Chowdhury
- Department of Biological Sciences, Birla Institute of Technology and Science (BITS), Pilani, Rajasthan, India
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7
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Hu Z, Yuan L, Yang X, Yi C, Lu J. The roles of long non-coding RNAs in ovarian cancer: from functions to therapeutic implications. Front Oncol 2024; 14:1332528. [PMID: 38725621 PMCID: PMC11079149 DOI: 10.3389/fonc.2024.1332528] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Accepted: 03/27/2024] [Indexed: 05/12/2024] Open
Abstract
Long non-coding RNAs (lncRNAs) are multifunctional and participate in a variety of biological processes and gene regulatory networks. The deregulation of lncRNAs has been extensively implicated in diverse human diseases, especially in cancers. Overwhelming evidence demonstrates that lncRNAs are essential to the pathophysiological processes of ovarian cancer (OC), acting as regulators involved in metastasis, cell death, chemoresistance, and tumor immunity. In this review, we illustrate the expanded functions of lncRNAs in the initiation and progression of OC and elaborate on the signaling pathways in which they pitch. Additionally, the potential clinical applications of lncRNAs as biomarkers in the diagnosis and treatment of OC were emphasized, cementing the bridge of communication between clinical practice and basic research.
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Affiliation(s)
- Zhong Hu
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Yangtze University, Jingzhou, Hubei, China
| | - Lijin Yuan
- Department of Obstetrics and Gynecology, Huangshi Puren Hospital, Huangshi, Hubei, China
| | - Xiu Yang
- Department of Obstetrics and Gynecology, Huangshi Central Hospital, Huangshi, Hubei, China
| | - Cunjian Yi
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Yangtze University, Jingzhou, Hubei, China
| | - Jinzhi Lu
- Department of Laboratory Medicine, The First Affiliated Hospital of Yangtze University, Jingzhou, Hubei, China
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Liu J, Xiao Y, Cao L, Lu S, Zhang S, Yang R, Wang Y, Zhang N, Yu Y, Wang X, Guo W, Wang Z, Xu H, Xing C, Song X, Cao L. Insights on E1-like enzyme ATG7: functional regulation and relationships with aging-related diseases. Commun Biol 2024; 7:382. [PMID: 38553562 PMCID: PMC10980737 DOI: 10.1038/s42003-024-06080-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2023] [Accepted: 03/20/2024] [Indexed: 04/02/2024] Open
Abstract
Autophagy is a dynamic self-renovation biological process that maintains cell homeostasis and is responsible for the quality control of proteins, organelles, and energy metabolism. The E1-like ubiquitin-activating enzyme autophagy-related gene 7 (ATG7) is a critical factor that initiates classic autophagy reactions by promoting the formation and extension of autophagosome membranes. Recent studies have identified the key functions of ATG7 in regulating the cell cycle, apoptosis, and metabolism associated with the occurrence and development of multiple diseases. This review summarizes how ATG7 is precisely programmed by genetic, transcriptional, and epigenetic modifications in cells and the relationship between ATG7 and aging-related diseases.
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Affiliation(s)
- Jingwei Liu
- The College of Basic Medical Science, Health Sciences Institute, China Medical University, Shenyang, Liaoning, China
- Key Laboratory of Cell Biology of Ministry of Public Health, Key Laboratory of Medical Cell Biology of Ministry of Education, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors (China Medical University), Ministry of Education, Liaoning Province Collaborative Innovation Center of Aging Related Disease Diagnosis and Treatment and Prevention, China Medical University, Shenyang, Liaoning, China
- Department of Anus and Intestine Surgery, First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China
| | - Yutong Xiao
- The College of Basic Medical Science, Health Sciences Institute, China Medical University, Shenyang, Liaoning, China
- Key Laboratory of Cell Biology of Ministry of Public Health, Key Laboratory of Medical Cell Biology of Ministry of Education, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors (China Medical University), Ministry of Education, Liaoning Province Collaborative Innovation Center of Aging Related Disease Diagnosis and Treatment and Prevention, China Medical University, Shenyang, Liaoning, China
| | - Liangzi Cao
- The College of Basic Medical Science, Health Sciences Institute, China Medical University, Shenyang, Liaoning, China
- Key Laboratory of Cell Biology of Ministry of Public Health, Key Laboratory of Medical Cell Biology of Ministry of Education, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors (China Medical University), Ministry of Education, Liaoning Province Collaborative Innovation Center of Aging Related Disease Diagnosis and Treatment and Prevention, China Medical University, Shenyang, Liaoning, China
| | - Songming Lu
- The College of Basic Medical Science, Health Sciences Institute, China Medical University, Shenyang, Liaoning, China
- Key Laboratory of Cell Biology of Ministry of Public Health, Key Laboratory of Medical Cell Biology of Ministry of Education, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors (China Medical University), Ministry of Education, Liaoning Province Collaborative Innovation Center of Aging Related Disease Diagnosis and Treatment and Prevention, China Medical University, Shenyang, Liaoning, China
| | - Siyi Zhang
- The College of Basic Medical Science, Health Sciences Institute, China Medical University, Shenyang, Liaoning, China
- Key Laboratory of Cell Biology of Ministry of Public Health, Key Laboratory of Medical Cell Biology of Ministry of Education, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors (China Medical University), Ministry of Education, Liaoning Province Collaborative Innovation Center of Aging Related Disease Diagnosis and Treatment and Prevention, China Medical University, Shenyang, Liaoning, China
| | - Ruohan Yang
- The College of Basic Medical Science, Health Sciences Institute, China Medical University, Shenyang, Liaoning, China
- Key Laboratory of Cell Biology of Ministry of Public Health, Key Laboratory of Medical Cell Biology of Ministry of Education, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors (China Medical University), Ministry of Education, Liaoning Province Collaborative Innovation Center of Aging Related Disease Diagnosis and Treatment and Prevention, China Medical University, Shenyang, Liaoning, China
| | - Yubang Wang
- The College of Basic Medical Science, Health Sciences Institute, China Medical University, Shenyang, Liaoning, China
- Key Laboratory of Cell Biology of Ministry of Public Health, Key Laboratory of Medical Cell Biology of Ministry of Education, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors (China Medical University), Ministry of Education, Liaoning Province Collaborative Innovation Center of Aging Related Disease Diagnosis and Treatment and Prevention, China Medical University, Shenyang, Liaoning, China
| | - Naijin Zhang
- The College of Basic Medical Science, Health Sciences Institute, China Medical University, Shenyang, Liaoning, China
- Department of Cardiology, First Hospital of China Medical University, Key Laboratory of Environmental Stress and Chronic Disease Control and Prevention, Ministry of Education, China Medical University, Shenyang, Liaoning, China
| | - Yang Yu
- The College of Basic Medical Science, Health Sciences Institute, China Medical University, Shenyang, Liaoning, China
- Key Laboratory of Cell Biology of Ministry of Public Health, Key Laboratory of Medical Cell Biology of Ministry of Education, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors (China Medical University), Ministry of Education, Liaoning Province Collaborative Innovation Center of Aging Related Disease Diagnosis and Treatment and Prevention, China Medical University, Shenyang, Liaoning, China
| | - Xiwen Wang
- Department of Thoracic Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| | - Wendong Guo
- The College of Basic Medical Science, Health Sciences Institute, China Medical University, Shenyang, Liaoning, China
- Key Laboratory of Cell Biology of Ministry of Public Health, Key Laboratory of Medical Cell Biology of Ministry of Education, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors (China Medical University), Ministry of Education, Liaoning Province Collaborative Innovation Center of Aging Related Disease Diagnosis and Treatment and Prevention, China Medical University, Shenyang, Liaoning, China
| | - Zhuo Wang
- The College of Basic Medical Science, Health Sciences Institute, China Medical University, Shenyang, Liaoning, China
- Key Laboratory of Cell Biology of Ministry of Public Health, Key Laboratory of Medical Cell Biology of Ministry of Education, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors (China Medical University), Ministry of Education, Liaoning Province Collaborative Innovation Center of Aging Related Disease Diagnosis and Treatment and Prevention, China Medical University, Shenyang, Liaoning, China
| | - Hongde Xu
- The College of Basic Medical Science, Health Sciences Institute, China Medical University, Shenyang, Liaoning, China.
- Key Laboratory of Cell Biology of Ministry of Public Health, Key Laboratory of Medical Cell Biology of Ministry of Education, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors (China Medical University), Ministry of Education, Liaoning Province Collaborative Innovation Center of Aging Related Disease Diagnosis and Treatment and Prevention, China Medical University, Shenyang, Liaoning, China.
| | - Chengzhong Xing
- Department of Anus and Intestine Surgery, First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.
| | - Xiaoyu Song
- The College of Basic Medical Science, Health Sciences Institute, China Medical University, Shenyang, Liaoning, China.
- Key Laboratory of Cell Biology of Ministry of Public Health, Key Laboratory of Medical Cell Biology of Ministry of Education, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors (China Medical University), Ministry of Education, Liaoning Province Collaborative Innovation Center of Aging Related Disease Diagnosis and Treatment and Prevention, China Medical University, Shenyang, Liaoning, China.
| | - Liu Cao
- The College of Basic Medical Science, Health Sciences Institute, China Medical University, Shenyang, Liaoning, China.
- Key Laboratory of Cell Biology of Ministry of Public Health, Key Laboratory of Medical Cell Biology of Ministry of Education, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors (China Medical University), Ministry of Education, Liaoning Province Collaborative Innovation Center of Aging Related Disease Diagnosis and Treatment and Prevention, China Medical University, Shenyang, Liaoning, China.
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9
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Xu H, Xiong W, Liu X, Wang Y, Shi M, Shi Y, Shui J, Yu Y. Long noncoding RNA LINC00921 serves as a predictive biomarker for lung adenocarcinoma: An observational study. Medicine (Baltimore) 2024; 103:e37179. [PMID: 38363898 PMCID: PMC10869092 DOI: 10.1097/md.0000000000037179] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2023] [Accepted: 01/17/2024] [Indexed: 02/18/2024] Open
Abstract
Lung adenocarcinoma (LUAD) is usually diagnosed at advanced stages. Hence, there is an urgent need to seek an effective biomarker to predict LUAD status. Long noncoding RNAs (lncRNAs) play key roles in the development of tumors. However, the relationship between LINC00921 and LUAD remains unclear. The gene expression data of LUAD were downloaded from the Cancer Genome Atlas database to investigate the expression level of LINC00921 in LUAD. Diagnostic ability analysis, survival analysis, tumor mutational burden analysis, and immune cell infiltration analysis of LINC00921 in LUAD patients were performed simultaneously. According to the median expression value of LINC00921, patients were divided into LINC00921 high- and low-expression groups. The function of LINC00921 in LUAD was identified through difference analysis and enrichment analysis. Moreover, drugs that may be relevant to LUAD treatment were screened. Finally, blood samples were collected for real-time polymerase chain reaction. LINC00921 was significantly lower in LUAD tumor tissues. Notably, patients with low expression of LINC00921 had a shorter median survival time. Decreased immune cell infiltration in the tumor microenvironment in the low LINC00921 expression group may contribute to poorer patient outcomes. Tumor mutational burden was significantly different in survival between the LINC00921 high- and low-expression groups. In addition, LINC00921 may exert an influence on cancer development through its regulation of target genes transcription. Glyceraldehyde-3-phosphate dehydrogenase-related drugs may be more likely to be therapeutically effective in LUAD. LINC00921 was able to be used as the potential diagnostic indicator for LUAD.
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Affiliation(s)
- Hongyu Xu
- Department of Oncology, 363 Hospital, Chengdu, Sichuan 610041, P.R. China
| | - Weijie Xiong
- Cancer Prevention and Treatment Institute of Chengdu, Department of Oncology, Chengdu Fifth People’s Hospital (The Second Clinical Medical College, Affiliated Fifth People’s Hospital of Chengdu University of Traditional Chinese Medicine), Chengdu, Sichuan, 610031, P.R. China
| | - Xianguo Liu
- Department of Oncology, 363 Hospital, Chengdu, Sichuan 610041, P.R. China
| | - Yang Wang
- Department of Oncology, 363 Hospital, Chengdu, Sichuan 610041, P.R. China
| | - Maolin Shi
- Department of Oncology, 363 Hospital, Chengdu, Sichuan 610041, P.R. China
| | - Yuhui Shi
- Department of Oncology, 363 Hospital, Chengdu, Sichuan 610041, P.R. China
| | - Jia Shui
- Department of Oncology, 363 Hospital, Chengdu, Sichuan 610041, P.R. China
| | - Yanxin Yu
- Department of Oncology, 363 Hospital, Chengdu, Sichuan 610041, P.R. China
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10
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Yang X, Xiong S, Zhao X, Jin J, Yang X, Du Y, Zhao L, He Z, Gong C, Guo L, Liang T. Orchestrating Cellular Balance: ncRNAs and RNA Interactions at the Dominant of Autophagy Regulation in Cancer. Int J Mol Sci 2024; 25:1561. [PMID: 38338839 PMCID: PMC10855840 DOI: 10.3390/ijms25031561] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Revised: 12/15/2023] [Accepted: 01/22/2024] [Indexed: 02/12/2024] Open
Abstract
Autophagy, a complex and highly regulated cellular process, is critical for the maintenance of cellular homeostasis by lysosomal degradation of cellular debris, intracellular pathogens, and dysfunctional organelles. It has become an interesting and attractive topic in cancer because of its dual role as a tumor suppressor and cell survival mechanism. As a highly conserved pathway, autophagy is strictly regulated by diverse non-coding RNAs (ncRNAs), ranging from short and flexible miRNAs to lncRNAs and even circRNAs, which largely contribute to autophagy regulatory networks via complex RNA interactions. The potential roles of RNA interactions during autophagy, especially in cancer procession and further anticancer treatment, will aid our understanding of related RNAs in autophagy in tumorigenesis and cancer treatment. Herein, we mainly summarized autophagy-related mRNAs and ncRNAs, also providing RNA-RNA interactions and their potential roles in cancer prognosis, which may deepen our understanding of the relationships between various RNAs during autophagy and provide new insights into autophagy-related therapeutic strategies in personalized medicine.
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Affiliation(s)
- Xueni Yang
- State Key Laboratory of Organic Electronics and Information Displays & Institute of Advanced Materials (IAM), Nanjing University of Posts & Telecommunications, Nanjing 210023, China; (X.Y.); (S.X.); (X.Z.); (J.J.); (L.Z.); (Z.H.)
| | - Shizheng Xiong
- State Key Laboratory of Organic Electronics and Information Displays & Institute of Advanced Materials (IAM), Nanjing University of Posts & Telecommunications, Nanjing 210023, China; (X.Y.); (S.X.); (X.Z.); (J.J.); (L.Z.); (Z.H.)
| | - Xinmiao Zhao
- State Key Laboratory of Organic Electronics and Information Displays & Institute of Advanced Materials (IAM), Nanjing University of Posts & Telecommunications, Nanjing 210023, China; (X.Y.); (S.X.); (X.Z.); (J.J.); (L.Z.); (Z.H.)
| | - Jiaming Jin
- State Key Laboratory of Organic Electronics and Information Displays & Institute of Advanced Materials (IAM), Nanjing University of Posts & Telecommunications, Nanjing 210023, China; (X.Y.); (S.X.); (X.Z.); (J.J.); (L.Z.); (Z.H.)
| | - Xinbing Yang
- Jiangsu Key Laboratory for Molecular and Medical Biotechnology, School of Life Science, Nanjing Normal University, Nanjing 210023, China; (X.Y.); (Y.D.)
| | - Yajing Du
- Jiangsu Key Laboratory for Molecular and Medical Biotechnology, School of Life Science, Nanjing Normal University, Nanjing 210023, China; (X.Y.); (Y.D.)
| | - Linjie Zhao
- State Key Laboratory of Organic Electronics and Information Displays & Institute of Advanced Materials (IAM), Nanjing University of Posts & Telecommunications, Nanjing 210023, China; (X.Y.); (S.X.); (X.Z.); (J.J.); (L.Z.); (Z.H.)
| | - Zhiheng He
- State Key Laboratory of Organic Electronics and Information Displays & Institute of Advanced Materials (IAM), Nanjing University of Posts & Telecommunications, Nanjing 210023, China; (X.Y.); (S.X.); (X.Z.); (J.J.); (L.Z.); (Z.H.)
| | - Chengjun Gong
- State Key Laboratory of Organic Electronics and Information Displays & Institute of Advanced Materials (IAM), Nanjing University of Posts & Telecommunications, Nanjing 210023, China; (X.Y.); (S.X.); (X.Z.); (J.J.); (L.Z.); (Z.H.)
| | - Li Guo
- State Key Laboratory of Organic Electronics and Information Displays & Institute of Advanced Materials (IAM), Nanjing University of Posts & Telecommunications, Nanjing 210023, China; (X.Y.); (S.X.); (X.Z.); (J.J.); (L.Z.); (Z.H.)
| | - Tingming Liang
- Jiangsu Key Laboratory for Molecular and Medical Biotechnology, School of Life Science, Nanjing Normal University, Nanjing 210023, China; (X.Y.); (Y.D.)
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11
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Elhelaly M, Shaker OG, Ayeldeen G, Elsergany AR, Mostafa N. Breast cancer risk is associated with the HULC rs7763881, MTMR3 rs12537 polymorphisms, and serum levels of HULC and MTMR3 in Egyptian patients. Mol Biol Rep 2023; 50:10073-10081. [PMID: 37910386 PMCID: PMC10676311 DOI: 10.1007/s11033-023-08897-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2023] [Accepted: 10/04/2023] [Indexed: 11/03/2023]
Abstract
BACKGROUND Highly upregulated in liver cancer (HULC) is one of the LncRNAs that was documented to enhance cancer progression, and its downregulation is associated with cell cycle arrest and apoptosis. Myotubularin-related protein 3 (MTMR3) is required for autophagy, and many studies consider MTMR3 to be a negative regulator of autophagy processes. However, nothing is understood about how they regulate breast cancer. MATERIAL AND METHODS This case-control study included 245 patients (Group A: 85 early BC Group B: 40 metastatic BC cases, Group C: 40 fibroadenoma cases; and Group D: 80 age matched healthy control subjects. TaqMan Real-time PCR was used to analyse rs7158663 and rs12537. MTMR3 and HULC gene expression levels were measured using RT-PCR. RESULT Breast cancer patients exhibited elevated serum MTMR3 and HULC compared to fibroadenomas and control cases. The MTMR3 rs12537 "T/T" genotype was highly expressed in cases of breast cancer (early and metastatic) compared to controls (risk genotype). On the other hand, the HULC rs7158663 genotypes were not statistically associated with breast cancer. However, when compared to the control, the C/C genotype of the HULC gene is higher in the case.MTMR3 gene expression was higher in the T/T genotype compared to both the C/C and C/T genotypes, while HULC gene expression was lower in the A/C genotype compared to both the A/A and C/C genotypes. Positive correlation between MTMR3 and HULC. MTMR3 and ALT, as well as HULC and alkaline phosphatase, both showed a statistically significant positive correlation. CONCLUSION Our findings reveal that MTMR3 and HULC serum expression and their SNPs (HULC rs7763881, MTMR3 rs12537) are associated with a higher risk for the development of breast cancer in the Egyptian population.
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Affiliation(s)
- Mona Elhelaly
- Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
| | - Olfat G Shaker
- Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ghada Ayeldeen
- Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Alyaa R Elsergany
- Internal Medicine Department, Medical Oncology Unit, Oncology Center, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Nora Mostafa
- Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
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12
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Saadh MJ, Almoyad MAA, Arellano MTC, Maaliw RR, Castillo-Acobo RY, Jalal SS, Gandla K, Obaid M, Abdulwahed AJ, Ibrahem AA, Sârbu I, Juyal A, Lakshmaiya N, Akhavan-Sigari R. Long non-coding RNAs: controversial roles in drug resistance of solid tumors mediated by autophagy. Cancer Chemother Pharmacol 2023; 92:439-453. [PMID: 37768333 DOI: 10.1007/s00280-023-04582-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2023] [Accepted: 08/12/2023] [Indexed: 09/29/2023]
Abstract
Current genome-wide studies have indicated that a great number of long non-coding RNAs (lncRNAs) are transcribed from the human genome and appeared as crucial regulators in a variety of cellular processes. Many studies have displayed a significant function of lncRNAs in the regulation of autophagy. Autophagy is a macromolecular procedure in cells in which intracellular substrates and damaged organelles are broken down and recycled to relieve cell stress resulting from nutritional deprivation, irradiation, hypoxia, and cytotoxic agents. Autophagy can be a double-edged sword and play either a protective or a damaging role in cells depending on its activation status and other cellular situations, and its dysregulation is related to tumorigenesis in various solid tumors. Autophagy induced by various therapies has been shown as a unique mechanism of resistance to anti-cancer drugs. Growing evidence is showing the important role of lncRNAs in modulating drug resistance via the regulation of autophagy in a variety of cancers. The role of lncRNAs in drug resistance of cancers is controversial; they may promote or suppress drug resistance via either activation or inhibition of autophagy. Mechanisms by which lncRNAs regulate autophagy to affect drug resistance are different, mainly mediated by the negative regulation of micro RNAs. In this review, we summarize recent studies that investigated the role of lncRNAs/autophagy axis in drug resistance of different types of solid tumors.
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Affiliation(s)
- Mohamed J Saadh
- Faculty of Pharmacy, Middle East University, Amman, 11831, Jordan
- Applied Science Research Center, Applied Science Private University, Amman, 11831, Jordan
| | | | | | - Renato R Maaliw
- College of Engineering, Southern Luzon State University, Lucban, Quezon, Philippines
| | | | - Sarah Salah Jalal
- College of Nursing, National University of Science and Technology, Dhi Qar, Iraq
| | - Kumaraswamy Gandla
- Department of Pharmaceutical Analysis, University of Chaitanya, Hanamkonda, India
| | | | | | - Azher A Ibrahem
- Department of Pharmacy, Al-Zahrawi University College, Karbala, Iraq
| | - Ioan Sârbu
- 2nd Department of Surgery-Pediatric Surgery and Orthopedics, "Grigore T. Popa" University of Medicine and Pharmacy, 700115, Iași, Romania.
| | - Ashima Juyal
- Department of Electronics & Communication Engineering, Uttaranchal Institute of Technology, Uttaranchal University, Dehradun, 248007, India
| | - Natrayan Lakshmaiya
- Department of Mechanical Engineering, Saveetha School of Engineering, SIMATS, Chennai, Tamil Nadu, India
| | - Reza Akhavan-Sigari
- Department of Neurosurgery, University Medical Center Tuebingen, Tübingen, Germany
- Department of Health Care Management and Clinical Research, Collegium Humanum Warsaw Management University Warsaw, Warsaw, Poland
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13
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Wang Y, Fu Y, Lu Y, Chen S, Zhang J, Liu B, Yuan Y. Unravelling the complexity of lncRNAs in autophagy to improve potential cancer therapy. Biochim Biophys Acta Rev Cancer 2023; 1878:188932. [PMID: 37329993 DOI: 10.1016/j.bbcan.2023.188932] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Revised: 05/30/2023] [Accepted: 06/10/2023] [Indexed: 06/19/2023]
Abstract
Autophagy is well-known as an internal catabolic process that is evolutionarily conserved and performs the key biological function in maintaining cellular homeostasis. It is tightly controlled by several autophagy-related (ATG) proteins, which are closely associated with many types of human cancers. However, what has remained controversial is the janus roles of autophagy in cancer progression. Interestingly, the biological function of long non-coding RNAs (lncRNAs) in autophagy has been gradually understood in different types of human cancers. More recently, numerous studies have demonstrated that several lncRNAs may regulate some ATG proteins and autophagy-related signaling pathways to either activate or inhibit the autophagic process in cancer. Thus, in this review, we summarize the latest advance in the knowledge of the complicated relationships between lncRNAs and autophagy in cancer. Also, the in-depth dissection of the lncRNAs-autophagy-cancers axis involved in this review would shed new light on discovery of more potential cancer biomarkers and therapeutic targets in the future.
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Affiliation(s)
- Yi Wang
- Department of Thoracic Surgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Yuqi Fu
- Department of Thoracic Surgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Yingying Lu
- Department of Thoracic Surgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Siwei Chen
- Department of Thoracic Surgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Jin Zhang
- School of Pharmacy, Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong 518055, China.
| | - Bo Liu
- Department of Thoracic Surgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
| | - Yong Yuan
- Department of Thoracic Surgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
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14
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Yang D, Shi M, You Q, Zhang Y, Hu Z, Xu J, Cai Q, Zhu Z. Tumor- and metastasis-promoting roles of miR-488 inhibition via HULC enhancement and EZH2-mediated p53 repression in gastric cancer. Cell Biol Toxicol 2023; 39:1341-1358. [PMID: 36449143 DOI: 10.1007/s10565-022-09760-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Accepted: 08/26/2022] [Indexed: 12/02/2022]
Abstract
Dysregulation of microRNAs (miRNAs or miRs) is implicated in the development of gastric cancer (GC), which is possibly related to their roles in targeting tumor-suppressive or tumor-promoting genes. Herein, the current study was intended to ascertain the function of miR-488 and its modulatory mechanism in GC. Initially, human GC cells were assayed for their in vitro malignancy after miRNA gain- or loss-of-function and RNA interference or overexpression. Also, tumorigenesis and liver metastasis were evaluated in nude mouse models. Results demonstrated that miR-488 elevation suppressed GC (MKN-45 and OCUM-1) cell proliferation, migration, and invasiveness in vitro and reduced their tumorigenesis and liver metastasis in vivo. The luciferase assay identified that miR-488 bound to HULC and inhibited its expression. Furthermore, HULC could enhance EZH2-H3K27me3 enrichment at the p53 promoter region and epigenetically repress the p53 expression based on the data from RIP- and ChIP-qPCR assay. Additionally, HULC was validated to enhance GC growth and metastasis in vitro and in vivo. Overall, HULC re-expression elicited by miR-488 inhibition can enhance EZH2-H3K27me3 enrichment in the p53 promoter and repress the p53 expression, thus promoting the growth and metastasis of GC.
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Affiliation(s)
- Dejun Yang
- Department of Gastrointestinal Surgery, Second Affiliated Hospital of Naval Medical University, Huangpu District, No. 415 Fengyang Road, Shanghai, 200003, China
| | - Mengyao Shi
- Department of Gastrointestinal Surgery, Second Affiliated Hospital of Naval Medical University, Huangpu District, No. 415 Fengyang Road, Shanghai, 200003, China
| | - Qing You
- Department of Gastrointestinal Surgery, Second Affiliated Hospital of Naval Medical University, Huangpu District, No. 415 Fengyang Road, Shanghai, 200003, China
| | - Yu Zhang
- Department of Gastrointestinal Surgery, Second Affiliated Hospital of Naval Medical University, Huangpu District, No. 415 Fengyang Road, Shanghai, 200003, China
| | - Zunqi Hu
- Department of Gastrointestinal Surgery, Second Affiliated Hospital of Naval Medical University, Huangpu District, No. 415 Fengyang Road, Shanghai, 200003, China
| | - Jiapeng Xu
- Department of Gastrointestinal Surgery, Second Affiliated Hospital of Naval Medical University, Huangpu District, No. 415 Fengyang Road, Shanghai, 200003, China
| | - Qingping Cai
- Department of Gastrointestinal Surgery, Second Affiliated Hospital of Naval Medical University, Huangpu District, No. 415 Fengyang Road, Shanghai, 200003, China.
| | - Zhenxin Zhu
- Department of Gastrointestinal Surgery, Second Affiliated Hospital of Naval Medical University, Huangpu District, No. 415 Fengyang Road, Shanghai, 200003, China.
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15
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Abstract
Autophagy is a self-digestion process by which misfolded proteins and damaged organelles in eukaryotic cells are degraded to maintain cellular homeostasis. This process is involved in the tumorigenesis, metastasis, and chemoresistance of various tumors such as ovarian cancer (OC). Noncoding RNAs (ncRNAs), mainly including microRNAs, long noncoding RNAs, and circular RNAs, have been extensively investigated in cancer research for their roles in the regulation of autophagy. Recent studies have shown that in OC cells, ncRNAs can modulate the formation of autophagosomes, which affect tumor progression and chemoresistance. An understanding of the role of autophagy in OC progression, treatment, and prognosis is important, and the identification of the regulatory roles of ncRNAs in autophagy leads to intervention strategies for OC therapy. This review summarizes the role of autophagy in OC and discusses the role of ncRNA-mediated autophagy in OC, as an understanding of these roles may contribute to the development of potential therapeutic strategies for this disease.
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Affiliation(s)
- Cong Feng
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin 150040, P.R. China
- Heilongjiang University of Chinese Medicine, Harbin 150040, P.R. China
| | - Xingxing Yuan
- Heilongjiang University of Chinese Medicine, Harbin 150040, P.R. China
- Department of Gastroenterology, Heilongjiang Academy of Traditional Chinese Medicine, Harbin 150001, P.R. China
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16
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Metur SP, Lei Y, Zhang Z, Klionsky DJ. Regulation of autophagy gene expression and its implications in cancer. J Cell Sci 2023; 136:jcs260631. [PMID: 37199330 PMCID: PMC10214848 DOI: 10.1242/jcs.260631] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/19/2023] Open
Abstract
Autophagy is a catabolic cellular process that targets and eliminates superfluous cytoplasmic components via lysosomal degradation. This evolutionarily conserved process is tightly regulated at multiple levels as it is critical for the maintenance of homeostasis. Research in the past decade has established that dysregulation of autophagy plays a major role in various diseases, such as cancer and neurodegeneration. However, modulation of autophagy as a therapeutic strategy requires identification of key players that can fine tune the induction of autophagy without complete abrogation. In this Review, we summarize the recent discoveries on the mechanism of regulation of ATG (autophagy related) gene expression at the level of transcription, post transcription and translation. Furthermore, we briefly discuss the role of aberrant expression of ATG genes in the context of cancer.
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Affiliation(s)
- Shree Padma Metur
- Life Sciences Institute and Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA
| | - Yuchen Lei
- Life Sciences Institute and Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA
| | - Zhihai Zhang
- Life Sciences Institute and Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA
| | - Daniel J. Klionsky
- Life Sciences Institute and Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA
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17
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Peng B, Li J, Yan Y, Liu Y, Liang Q, Liu W, Thakur A, Zhang K, Xu Z, Wang J, Zhang F. Non-coding RNAs: The recently accentuated molecules in the regulation of cell autophagy for ovarian cancer pathogenesis and therapeutic response. Front Pharmacol 2023; 14:1162045. [PMID: 37063265 PMCID: PMC10102359 DOI: 10.3389/fphar.2023.1162045] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2023] [Accepted: 03/20/2023] [Indexed: 04/03/2023] Open
Abstract
Autophagy is a self-recycling and conserved process, in which the senescent cytoplasmic components are degraded in cells and then recycled to maintain homeostatic balance. Emerging evidence has suggested the involvement of autophagy in oncogenesis and progression of various cancers, such as ovarian cancer (OC). Meanwhile, the non-coding RNAs (ncRNAs) frequently regulate the mRNA transcription and other functional signaling pathways in cell autophagy, displaying promising roles in human cancer pathogenesis and therapeutic response. This article mainly reviews the cutting-edge research advances about the interactions between ncRNAs and autophagy in OC. This review not only summarizes the underlying mechanisms of dynamic ncRNA-autophagy association in OC, but also discusses their prognostic implications and therapeutic biomarkers. The aim of this review was to provide a more in-depth knowledge framework exploring the ncRNA-autophagy crosstalk and highlight the promising treatment strategies for OC patients.
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Affiliation(s)
- Bi Peng
- Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Jing Li
- Department of Pharmacy, Shanghai Pudong New Area People’s Hospital, Shanghai, China
| | - Yuanliang Yan
- Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Yuanhong Liu
- Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Qiuju Liang
- Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Wei Liu
- Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Department of Orthopedic Surgery, The Second Hospital University of South China, Hengyang, Hunan, China
| | - Abhimanyu Thakur
- Ben May Department for Cancer Research, Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL, United States
| | - Kui Zhang
- State Key Laboratory of Silkworm Genome Biology, Medical Research Institute, Southwest University, Chongqing, China
| | - Zhijie Xu
- Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Jian Wang
- Department of Pharmacy, Shanghai Pudong New Area People’s Hospital, Shanghai, China
| | - Fan Zhang
- Department of Gynecology, Xiangya Hospital, Central South University, Changsha, Hunan, China
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18
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Zandieh MA, Farahani MH, Rajabi R, Avval ST, Karimi K, Rahmanian P, Razzazan M, Javanshir S, Mirzaei S, Paskeh MDA, Salimimoghadam S, Hushmandi K, Taheriazam A, Pandey V, Hashemi M. Epigenetic regulation of autophagy by non-coding RNAs in gastrointestinal tumors: Biological functions and therapeutic perspectives. Pharmacol Res 2023; 187:106582. [PMID: 36436707 DOI: 10.1016/j.phrs.2022.106582] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2022] [Revised: 11/21/2022] [Accepted: 11/23/2022] [Indexed: 11/26/2022]
Abstract
Cancer is the manifestation of changes and mutations in genetic and epigenetic levels. Non-coding RNAs (ncRNAs) are commonly dysregulated in disease pathogenesis, and their role in cancer has been well-documented. The ncRNAs regulate various molecular pathways and mechanisms in cancer that can lead to induction/inhibition of carcinogenesis. Autophagy is a molecular "self-digestion" mechanism its function can be pro-survival or pro-death in tumor cells. The aim of the present review is to evaluate the role of ncRNAs in regulating autophagy in gastrointestinal tumors. The role of the ncRNA/autophagy axis in affecting the progression of gastric, liver, colorectal, pancreatic, esophageal, and gallbladder cancers is investigated. Both ncRNAs and autophagy mechanisms can function as oncogenic or onco-suppressor and this interaction can determine the growth, invasion, and therapy response of gastrointestinal tumors. ncRNA/autophagy axis can reduce/increase the proliferation of gastrointestinal tumors via the glycolysis mechanism. Furthermore, related molecular pathways of metastasis, such as EMT and MMPs, are affected by the ncRNA/autophagy axis. The response of gastrointestinal tumors to chemotherapy and radiotherapy can be suppressed by pro-survival autophagy, and ncRNAs are essential regulators of this mechanism. miRNAs can regulate related genes and proteins of autophagy, such as ATGs and Beclin-1. Furthermore, lncRNAs and circRNAs down-regulate miRNA expression via sponging to modulate the autophagy mechanism. Moreover, anti-cancer agents can affect the expression level of ncRNAs regulating autophagy in gastrointestinal tumors. Therefore, translating these findings into clinics can improve the prognosis of patients.
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Affiliation(s)
- Mohammad Arad Zandieh
- Department of Food Hygiene and Quality Control, Division of Epidemiology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
| | - Melika Heydari Farahani
- Faculty of Veterinary Medicine, Islamic Azad University, Shahr-e kord Branch, Chaharmahal and Bakhtiari, Iran
| | - Romina Rajabi
- Faculty of Veterinary Medicine, Islamic Azad University, Science and Research Branch, Tehran, Iran
| | | | - Kimia Karimi
- Faculty of Veterinary Medicine, Islamic Azad University, Science and Research Branch, Tehran, Iran
| | - Parham Rahmanian
- Faculty of Veterinary Medicine, Islamic Azad University, Science and Research Branch, Tehran, Iran
| | - Mehrnaz Razzazan
- Medical Student, Student Research Committee, Golestan University of Medical Sciences, Gorgan, Iran
| | - Salar Javanshir
- Young Researchers and Elite Club, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Sepideh Mirzaei
- Department of Biology, Faculty of Science, Islamic Azad University, Science and Research Branch, Tehran, Iran
| | - Mahshid Deldar Abad Paskeh
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Shokooh Salimimoghadam
- Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran
| | - Kiavash Hushmandi
- Department of Food Hygiene and Quality Control, Division of Epidemiology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.
| | - Afshin Taheriazam
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Department of Orthopedics, Faculty of medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
| | - Vijay Pandey
- Precision Medicine and Healthcare Research Center, Tsinghua-Berkeley Shenzhen Institute, Tsinghua University, Shenzhen 518055, Guangdong, China; Institute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China.
| | - Mehrdad Hashemi
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
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19
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Effect of Long Noncoding RNA HULC on Proliferation, Migration, and Invasion of Osteosarcoma Cells. JOURNAL OF ONCOLOGY 2022; 2022:7526731. [PMID: 36213832 PMCID: PMC9546645 DOI: 10.1155/2022/7526731] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Revised: 09/02/2022] [Accepted: 09/15/2022] [Indexed: 11/18/2022]
Abstract
Background Previous studies had shown that lncRNA HULC exhibited different effects in human cancers. However, the role of HULC was not reported in osteosarcoma. Hence, we designed this research to explore the function of HULC in osteosarcoma. Methods Firstly, HULC expression was measured in osteosarcoma tissues and cells via the RT-qPCR assay. The protein expression was detected through western blot. Then, CCK-8 and Transwell assays were conducted to measure cell proliferation, migration, and invasion. Results The expression of HULC was obviously higher in osteosarcoma tissues and cells compared with normal control. Moreover, cell proliferation, migration, and invasion were inhibited by HULC knockdown in osteosarcoma cells. HULC overexpression markedly increased osteosarcoma cell proliferation and tumor size in vivo. Furthermore, HULC increased the activity of AKT-PI3K-mTOR pathway by blocking PTEN in osteosarcoma cells. LY294002 inhibited the phosphorylation of AKT, mTOR, and PI3K. Overexpressing HULC enhanced cell migration and invasion of SAOS-2 cells and MG63 cells, while LY294002 reversed the effects. Conclusion HULC enhanced the progression of osteosarcoma through targeting PTEN.
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20
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Xu H, Jiang C, Yao F, Liang H, Yan H, Chen D, Wu Y, Zhong L. Pan-Cancer Analysis Reveals the Relation between TRMT112 and Tumor Microenvironment. JOURNAL OF ONCOLOGY 2022; 2022:1445932. [PMID: 36081672 PMCID: PMC9448524 DOI: 10.1155/2022/1445932] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/21/2022] [Revised: 07/29/2022] [Accepted: 08/09/2022] [Indexed: 11/17/2022]
Abstract
Dysregulated epigenetic modifications play a critical role in cancer development where TRMT112 is a member of the transfer RNA (tRNA) methyltransferase family. Till now, no studies have revealed the linkage between TRMT112 expression and diverse types of tumors. Based on TCGA data, we first probed into the relation between TRMT112 and prognosis and the potential role of TRMT112 in tumor microenvironment across 33 types of tumor. TRMT112 presented with increased expression in most cancers, which was significantly prognostic. Furthermore, TRMT112 was associated with tumor-associated fibroblasts in a variety of cancers. Additionally, a positive relationship was identified between TRMT112 expression and multiple tumor-related immune infiltrations, such as dendritic cells, CD8+ T cells, macrophages, CD4+ T cells, neutrophils, and B cells in lung adenocarcinoma and breast invasive carcinoma. In summary, our results suggest that TRMT112 might be a potential prognostic predictor of cancers and involved in regulating multiple cancer-related immune responses to some extent.
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Affiliation(s)
- Haitao Xu
- Department of Hematology, Anqing Municipal Hospital, Anqing Medical Center Affiliated to Anhui Medical University, Anqing, China
| | - Caihong Jiang
- Department of Pediatric Surgery, Anqing Municipal Hospital, Anqing Medical Center Affiliated to Anhui Medical University, Anqing, China
| | - Fusheng Yao
- Department of Hematology, Anqing Municipal Hospital, Anqing Medical Center Affiliated to Anhui Medical University, Anqing, China
| | - Hong Liang
- Department of Hematology, Anqing Municipal Hospital, Anqing Medical Center Affiliated to Anhui Medical University, Anqing, China
| | - Hong Yan
- Department of Hematology, Anqing Municipal Hospital, Anqing Medical Center Affiliated to Anhui Medical University, Anqing, China
| | - Dangui Chen
- Department of Hematology, Anqing Municipal Hospital, Anqing Medical Center Affiliated to Anhui Medical University, Anqing, China
| | - Youzhi Wu
- Department of Hematology, Anqing Municipal Hospital, Anqing Medical Center Affiliated to Anhui Medical University, Anqing, China
| | - Long Zhong
- Department of Hematology, Anqing Municipal Hospital, Anqing Medical Center Affiliated to Anhui Medical University, Anqing, China
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21
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Haake SM, Plosa EJ, Kropski JA, Venton LA, Reddy A, Bock F, Chang BT, Luna AJ, Nabukhotna K, Xu ZQ, Prather RA, Lee S, Tanjore H, Polosukhin VV, Viquez OM, Jones A, Luo W, Wilson MH, Rathmell WK, Massion PP, Pozzi A, Blackwell TS, Zent R. Ligand-independent integrin β1 signaling supports lung adenocarcinoma development. JCI Insight 2022; 7:e154098. [PMID: 35763345 PMCID: PMC9462485 DOI: 10.1172/jci.insight.154098] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Accepted: 06/24/2022] [Indexed: 11/17/2022] Open
Abstract
Integrins - the principal extracellular matrix (ECM) receptors of the cell - promote cell adhesion, migration, and proliferation, which are key events for cancer growth and metastasis. To date, most integrin-targeted cancer therapeutics have disrupted integrin-ECM interactions, which are viewed as critical for integrin functions. However, such agents have failed to improve cancer patient outcomes. We show that the highly expressed integrin β1 subunit is required for lung adenocarcinoma development in a carcinogen-induced mouse model. Likewise, human lung adenocarcinoma cell lines with integrin β1 deletion failed to form colonies in soft agar and tumors in mice. Mechanistically, we demonstrate that these effects do not require integrin β1-mediated adhesion to ECM but are dependent on integrin β1 cytoplasmic tail-mediated activation of focal adhesion kinase (FAK). These studies support a critical role for integrin β1 in lung tumorigenesis that is mediated through constitutive, ECM binding-independent signaling involving the cytoplasmic tail.
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Affiliation(s)
- Scott M. Haake
- Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
- Department of Veterans Affairs, Nashville, Tennessee, USA
- Vanderbilt-Ingram Cancer Center, Nashville, Tennessee, USA
| | - Erin J. Plosa
- Division of Neonatology, Department of Pediatrics, Nashville, Tennessee, USA
| | - Jonathan A. Kropski
- Department of Veterans Affairs, Nashville, Tennessee, USA
- Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
- Department of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee, USA
| | - Lindsay A. Venton
- Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Anupama Reddy
- Vindhya Data Science, Morrisville, North Carolina, USA
| | - Fabian Bock
- Division of Nephrology and Hypertension, Department of Medicine, and
| | - Betty T. Chang
- Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Allen J. Luna
- Division of Nephrology and Hypertension, Department of Medicine, and
| | | | - Zhi-Qi Xu
- Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Rebecca A. Prather
- Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Sharon Lee
- Division of Nephrology and Hypertension, Department of Medicine, and
| | - Harikrishna Tanjore
- Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Vasiliy V. Polosukhin
- Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Olga M. Viquez
- Division of Nephrology and Hypertension, Department of Medicine, and
| | - Angela Jones
- Vanderbilt Technologies for Advanced Genomics (VANTAGE), Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Wentian Luo
- Division of Nephrology and Hypertension, Department of Medicine, and
| | - Matthew H. Wilson
- Department of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee, USA
- Division of Nephrology and Hypertension, Department of Medicine, and
| | - W. Kimryn Rathmell
- Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
- Vanderbilt-Ingram Cancer Center, Nashville, Tennessee, USA
| | - Pierre P. Massion
- Department of Veterans Affairs, Nashville, Tennessee, USA
- Vanderbilt-Ingram Cancer Center, Nashville, Tennessee, USA
- Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Ambra Pozzi
- Department of Veterans Affairs, Nashville, Tennessee, USA
- Vanderbilt-Ingram Cancer Center, Nashville, Tennessee, USA
- Division of Nephrology and Hypertension, Department of Medicine, and
| | - Timothy S. Blackwell
- Department of Veterans Affairs, Nashville, Tennessee, USA
- Vanderbilt-Ingram Cancer Center, Nashville, Tennessee, USA
- Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
- Department of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee, USA
| | - Roy Zent
- Department of Veterans Affairs, Nashville, Tennessee, USA
- Vanderbilt-Ingram Cancer Center, Nashville, Tennessee, USA
- Department of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee, USA
- Division of Nephrology and Hypertension, Department of Medicine, and
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22
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Li YP, Liu Y, Xiao LM, Chen LK, Tao EX, Zeng EM, Xu CH. Induction of cancer cell stemness in glioma through glycolysis and the long noncoding RNA HULC-activated FOXM1/AGR2/HIF-1α axis. J Transl Med 2022; 102:691-701. [PMID: 35013529 DOI: 10.1038/s41374-021-00664-9] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Revised: 08/17/2021] [Accepted: 08/20/2021] [Indexed: 11/09/2022] Open
Abstract
Gliomas are the most common primary intracranial tumor, accounting for more than 70% of brain malignancies. Studies indicate that highly upregulated in liver cancer (HULC), a long noncoding RNA (lncRNA), functions as an oncogene in gliomas. However, the underlying mechanism of HULC in gliomas remains under-studied and was subsequently investigated in the current study. Brain tissues were clinically collected from 50 patients with glioblastoma (GBM) and 35 patients with acute craniocerebral injury, followed by immunohistochemical detection of the expression patterns of Forkhead box M1 (FOXM1), anterior gradient 2 (AGR2), and hypoxia-inducible factor-1α (HIF-1α). After flow cytometry-based sorting of the CD133+ glioma stem cells (GSCs) from the U251 cell line, the obtained cells were subjected to lentivirus infection. Afterwards, the proliferation, stemness, and apoptosis of GSCs were evaluated using sphere formation, immunofluorescence, and flow cytometry assays, respectively. In addition, the interactions among HULC, FOXM1, AGR2, and HIF-1α were identified using RNA immunoprecipitation (RIP), RNA pull-down, Chromatin immunoprecipitation (ChIP), IP, and dual luciferase reporter assays. Last, the specific effects were validated in vivo. HULC was upregulated in GBM tissues and GSCs, which may promote the progression of glioma. On the other hand, silencing of HULC reduced the stemness, inhibited the proliferation, and promoted the apoptosis and differentiation of GSCs. In addition, HULC further stabilized FOXM1 expression in GSCs through ubiquitination, while FOXM1 activated AGR2 transcription to promote HIF-1α expression. Moreover, HULC promoted the glycolysis and stemness of GSCs through its regulation of the FOXM1/AGR2/HIF-1α axis, consequently exacerbating the occurrence and development of glioma. The findings obtained in our study indicate that HULC stabilizes the FOXM1 protein by ubiquitination to upregulate the expression of AGR2 and HIF-1α, which further promote the glycolysis of and maintain the stemness of GSCs, to enhance the tumorigenicity of GSCs, highlighting a novel therapeutic target for glioma.
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Affiliation(s)
- You-Ping Li
- Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, P.R. China
| | - Yue Liu
- Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, P.R. China
| | - Li-Min Xiao
- Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, P.R. China
| | - Li-Ke Chen
- Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, P.R. China
| | - Er-Xing Tao
- Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, P.R. China
| | - Er-Ming Zeng
- Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, P.R. China
| | - Chun-Hua Xu
- Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, P.R. China.
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Chowdhury SG, Bhattacharya D, Karmakar P. Exosomal long noncoding RNAs - the lead thespian behind the regulation, cause and cure of autophagy-related diseases. Mol Biol Rep 2022; 49:7013-7024. [PMID: 35655053 DOI: 10.1007/s11033-022-07514-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Revised: 04/06/2022] [Accepted: 04/25/2022] [Indexed: 11/26/2022]
Abstract
Recent advances in exosome biology have revealed significant roles of exosome and their contents in intercellular communication. Among various exosomal content, long non-coding RNAs (lncRNAs), which have a large size (˃ 200 nt) and lack protein coding potential, are known to play key roles in intercellular communication and novel biomarkers of various metabolic disorders. Moreover, long non-coding RNAs are often involved in the regulation of various cellular processes such as autophagy, apoptosis, cell proliferation. On the other hand, autophagy is the central regulating point that controls the various metabolic functions of the body. This process is known to prevent diseases and promote longevity. Therefore, the present review discusses the relationship between diseases and autophagy, and also look into the biological functions of exosome-associated lncRNAs in regulating autophagy. Furthermore, this review will summarize some of the studies that provide novel insights into the pathogenesis of autophagy-related diseases followed by the non-canonical roles played by autophagy and related proteins in the development of exosome biogenesis.
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Affiliation(s)
| | | | - Parimal Karmakar
- Department of Life Science and Biotechnology, Jadavpur University, 700032, Kolkata, India.
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24
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Song G, Shang C, Sun L, Li Y, Zhu Y, Xiu Z, Liu Z, Li Y, Yang X, Ge C, Fang J, Jin N, Li X. Ad-VT enhances the sensitivity of chemotherapy-resistant lung adenocarcinoma cells to gemcitabine and paclitaxel in vitro and in vivo. Invest New Drugs 2022; 40:274-289. [PMID: 34981275 PMCID: PMC8993744 DOI: 10.1007/s10637-021-01204-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Accepted: 11/30/2021] [Indexed: 10/31/2022]
Abstract
Background One of the main challenges in the clinical treatment of lung cancer is resistance to chemotherapeutic drugs. P-glycoprotein (P-gp)-mediated drug resistance is the main obstacle to successfully implementing microtubule-targeted tumor chemotherapy. Purpose In this study, we explored the effect of Ad-hTERTp-E1a-Apoptin (Ad-VT) on drug-resistant cell lines and the molecular mechanism by which Ad-VT combined with chemotherapy affects drug-resistant cells and parental cells. Methods In vitro, cell proliferation, colony formation, resistance index (RI), apoptosis and autophagy assays were performed. Protein expression was analyzed by Western blotting. Finally, a xenograft tumor model in nude mice was used to detect tumor growth and evaluate histological characteristics. Results Our results showed that Ad-VT had an obvious killing effect on A549, A549/GEM and A549/Paclitaxel cancer cells, and the sensitivity of drug-resistant cell lines to Ad-VT was significantly higher than that of parental A549 cells. Compared with A549 cells, A549/GEM and A549/Paclitaxel cells had higher autophagy levels and higher viral replication ability. Ad-VT decreased the levels of p-PI3k, p-Akt and p-mTOR and the expression of P-gp. In vivo, Ad-VT combined with chemotherapy can effectively inhibit the growth of chemotherapy-resistant tumors and prolong the survival of mice. Conclusions Thus, the combination of Ad-VT and chemotherapeutic drugs will be a promising strategy to overcome chemoresistance.
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Affiliation(s)
- Gaojie Song
- Medical College, Yanbian University, Yanji, China
- Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, China
- Academician Workstation of Jilin Province, Changchun University of Chinese Medicine, Changchun, China
| | - Chao Shang
- Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, China
| | - Lili Sun
- Department of Head and Neck Surgery, Tumor Hospital of Jilin Province, Changchun, China
| | - Yiquan Li
- Academician Workstation of Jilin Province, Changchun University of Chinese Medicine, Changchun, China
| | - Yilong Zhu
- Academician Workstation of Jilin Province, Changchun University of Chinese Medicine, Changchun, China
| | - Zhiru Xiu
- Academician Workstation of Jilin Province, Changchun University of Chinese Medicine, Changchun, China
| | - Zirui Liu
- Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, China
| | - Yaru Li
- Academician Workstation of Jilin Province, Changchun University of Chinese Medicine, Changchun, China
| | - Xia Yang
- Academician Workstation of Jilin Province, Changchun University of Chinese Medicine, Changchun, China
| | - Chenchen Ge
- Academician Workstation of Jilin Province, Changchun University of Chinese Medicine, Changchun, China
| | - Jinbo Fang
- Academician Workstation of Jilin Province, Changchun University of Chinese Medicine, Changchun, China.
| | - Ningyi Jin
- Medical College, Yanbian University, Yanji, China.
- Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, China.
- Academician Workstation of Jilin Province, Changchun University of Chinese Medicine, Changchun, China.
| | - Xiao Li
- Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, China.
- Academician Workstation of Jilin Province, Changchun University of Chinese Medicine, Changchun, China.
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25
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Lin X, Zhuang S, Chen X, Du J, Zhong L, Ding J, Wang L, Yi J, Hu G, Tang G, Luo X, Liu W, Ye F. lncRNA ITGB8-AS1 functions as a ceRNA to promote colorectal cancer growth and migration through integrin-mediated focal adhesion signaling. Mol Ther 2022; 30:688-702. [PMID: 34371180 PMCID: PMC8821934 DOI: 10.1016/j.ymthe.2021.08.011] [Citation(s) in RCA: 98] [Impact Index Per Article: 32.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Revised: 06/16/2021] [Accepted: 07/20/2021] [Indexed: 02/07/2023] Open
Abstract
Long non-coding RNAs (lncRNAs) play critical roles in tumorigenesis and progression of colorectal cancer (CRC). However, functions of most lncRNAs in CRC and their molecular mechanisms remain uncharacterized. Here we found that lncRNA ITGB8-AS1 was highly expressed in CRC. Knockdown of ITGB8-AS1 suppressed cell proliferation, colony formation, and tumor growth in CRC, suggesting oncogenic roles of ITGB8-AS1. Transcriptomic analysis followed by KEGG analysis revealed that focal adhesion signaling was the most significantly enriched pathway for genes positively regulated by ITGB8-AS1. Consistently, knockdown of ITGB8-AS1 attenuated the phosphorylation of SRC, ERK, and p38 MAPK. Mechanistically, ITGB8-AS1 could sponge miR-33b-5p and let-7c-5p/let-7d-5p to regulate the expression of integrin family genes ITGA3 and ITGB3, respectively, in the cytosol of cells. Targeting ITGB8-AS1 using antisense oligonucleotide (ASO) markedly reduced cell proliferation and tumor growth in CRC, indicating the therapeutic potential of ITGB8-AS1 in CRC. Furthermore, ITGB8-AS1 was easily detected in plasma of CRC patients, which was positively correlated with differentiation and TNM stage, as well as plasma levels of ITGA3 and ITGB3. In conclusion, ITGB8-AS1 functions as a competing endogenous RNA (ceRNA) to regulate cell proliferation and tumor growth of CRC via regulating focal adhesion signaling. Targeting ITGB8-AS1 is effective in suppressing CRC cell growth and tumor growth. Elevated plasma levels of ITGB8-AS1 were detected in advanced-stage CRC. Thus, ITGB8-AS1 could serve as a potential therapeutic target and circulating biomarker in CRC.
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Affiliation(s)
- Xiaoting Lin
- Department of Medical Oncology, Xiamen Key Laboratory of Antitumor Drug Transformation Research, the First Affiliated Hospital of Xiamen University, Xiamen 361003, China,Department of Clinical Medicine, Fujian Medical University, Fuzhou 350122, China
| | - Shiwen Zhuang
- Department of Medical Oncology, Xiamen Key Laboratory of Antitumor Drug Transformation Research, the First Affiliated Hospital of Xiamen University, Xiamen 361003, China,Department of Clinical Medicine, Fujian Medical University, Fuzhou 350122, China
| | - Xue Chen
- Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361104, China
| | - Jun Du
- Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361104, China
| | - Longhua Zhong
- Department of Medical Oncology, Xiamen Key Laboratory of Antitumor Drug Transformation Research, the First Affiliated Hospital of Xiamen University, Xiamen 361003, China
| | - Jiancheng Ding
- Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361104, China
| | - Lei Wang
- Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361104, China
| | - Jia Yi
- Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361104, China
| | - Guosheng Hu
- Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361104, China
| | - Guohui Tang
- Department of Anus and Bowels, Affiliated Nanhua Hospital, University of South China, Hengyang 421010, China
| | - Xi Luo
- BE/Phase I Clinical Center, First Affiliated Hospital of Xiamen University, Xiamen 361003 China,Corresponding author: Xi Luo, BE/Phase I Clinical Center, First Affiliated Hospital of Xiamen University, Xiamen 361003 China.
| | - Wen Liu
- Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361104, China,Corresponding author: Wen Liu, Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361104, China.
| | - Feng Ye
- Department of Medical Oncology, Xiamen Key Laboratory of Antitumor Drug Transformation Research, the First Affiliated Hospital of Xiamen University, Xiamen 361003, China,Department of Clinical Medicine, Fujian Medical University, Fuzhou 350122, China,Corresponding author: Feng Ye, Department of Clinical Medicine, Fujian Medical University, Fuzhou 350122, China.
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26
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Abdi E, Latifi-Navid S, Latifi-Navid H. Long noncoding RNA polymorphisms and colorectal cancer risk: Progression and future perspectives. ENVIRONMENTAL AND MOLECULAR MUTAGENESIS 2022; 63:98-112. [PMID: 35275417 DOI: 10.1002/em.22477] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Revised: 02/25/2022] [Accepted: 03/08/2022] [Indexed: 06/14/2023]
Abstract
Colorectal cancer (CRC) is one of the most common cancers causing death worldwide. Many long noncoding RNAs (lncRNAs) have possible carcinogenic or tumor suppressor functions. Some lncRNA polymorphisms are useful for predicting cancer risk, and may help advance personalized therapy management. While the use of lncRNAs as biomarkers is promising, there are still drawbacks, and further studies are needed to verify the consistency of current outcomes in large-scale populations and different ethnicities. Single nucleotide polymorphisms (SNPs) can disrupt a lncRNAs' function, thus enhancing or hindering disease occurrence. SNPs can directly influence the lncRNA expression by interfering with transcription factor binding or affecting indirectly a regulatory factors' expression. Moreover, the association between lncRNAs and other RNAs or proteins may be disrupted by SNPs. This research sought to assess the association between lncRNA polymorphisms and CRC risk, as well as clinical and therapeutic consequences in certain cases.
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Affiliation(s)
- Esmat Abdi
- Department of Biology, Faculty of Sciences, University of Mohaghegh Ardabili, Ardabil, Iran
| | - Saeid Latifi-Navid
- Department of Biology, Faculty of Sciences, University of Mohaghegh Ardabili, Ardabil, Iran
| | - Hamid Latifi-Navid
- Department of Molecular Medicine, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran
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27
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Sun Y, Cao X, Guo Y, Liu B, Zhang Y. The Prognostic and Molecular Landscape of Autophagy-Related Long Noncoding RNA in Colorectal Cancer. BIOMED RESEARCH INTERNATIONAL 2022; 2022:5614915. [PMID: 35097120 PMCID: PMC8794669 DOI: 10.1155/2022/5614915] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Accepted: 11/18/2021] [Indexed: 12/12/2022]
Abstract
Current evidence suggests that autophagy is closely correlated with the pathogenesis and development of malignant tumors. This study is aimed at assessing the potential prognostic significance of autophagy-related long noncoding RNA (ARlncRNA) in colorectal cancer (CRC). 3145 ARlncRNAs were obtained from autophagy-related genes (ARGs) by Pearson correlation analysis, and we established a competing endogenous RNA (ceRNA) network mediated by ARlncRNAs. A novel six-ARlncRNA prognostic signature was constructed based on TCGA samples used as the training group. Kaplan-Meier survival analysis and independent prognosis analysis were performed on the internal (training and test groups) and external validations (GEO datasets) to assess the accuracy and clinical practicability. Moreover, the nomogram combining the two independent prognostic factors (age and ARlncRNA-risk score (ARlncRNA-RS)) intuitively displayed overall survival. Gene set enrichment analysis (GSEA) conducted on the prognostic signature revealed that the gene set of the high-risk group was significantly enriched in the hallmark gene set "hypoxia" and the gene set of the low-risk group was enriched in KEGG pathways, including "peroxisome," "the citrate cycle (TCA cycle)," and "other glycan degradation." Assessment of antineoplastic therapy susceptibility and microsatellite instability (MSI) analysis were performed on CRC samples based on the prognostic signature. Moreover, Spearman correlation analysis was conducted on the expression of six ARlncRNAs of the prognostic signature and cancer stem cell (CSC) index as well as the tumor microenvironment (TME). In conclusion, this study established a six-ARlncRNA prognostic signature, which yielded favorable prognostic significance and demonstrated the correlation between ARlncRNAs and CRC progression.
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Affiliation(s)
- YuanLin Sun
- Department of Gastrointestinal Surgery, First Hospital of Jilin University, Changchun, 130021 Jilin, China
| | - XueYuan Cao
- Department of Gastrointestinal Surgery, First Hospital of Jilin University, Changchun, 130021 Jilin, China
| | - YuChen Guo
- Department of Gastrointestinal Surgery, First Hospital of Jilin University, Changchun, 130021 Jilin, China
| | - Bin Liu
- Department of Gastrointestinal Surgery, First Hospital of Jilin University, Changchun, 130021 Jilin, China
| | - Yang Zhang
- Department of Gastrointestinal Surgery, First Hospital of Jilin University, Changchun, 130021 Jilin, China
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Honarmand Tamizkar K, Gorji P, Gholipour M, Hussen BM, Mazdeh M, Eslami S, Taheri M, Ghafouri-Fard S. Parkinson's Disease Is Associated With Dysregulation of Circulatory Levels of lncRNAs. Front Immunol 2021; 12:763323. [PMID: 34868009 PMCID: PMC8632636 DOI: 10.3389/fimmu.2021.763323] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Accepted: 10/22/2021] [Indexed: 11/21/2022] Open
Abstract
Long non-coding RNAs (lncRNAs) have been recently reported to be involved in the pathoetiology of Parkinson’s disease (PD). Circulatory levels of lncRNAs might be used as markers for PD. In the present work, we measured expression levels of HULC, PVT1, MEG3, SPRY4-IT1, LINC-ROR and DSCAM-AS1 lncRNAs in the circulation of patients with PD versus healthy controls. Expression of HULC was lower in total patients compared with total controls (Expression ratio (ER)=0.19, adjusted P value<0.0001) as well as in female patients compared with female controls (ER=0.071, adjusted P value=0.0004). Expression of PVT1 was lower in total patients compared with total controls (ER=0.55, adjusted P value=0.0124). Expression of DSCAM-AS1 was higher in total patients compared with total controls (ER=5.67, P value=0.0029) and in male patients compared with male controls (ER=9.526, adjusted P value=0.0024). Expression of SPRY4-IT was higher in total patients compared with total controls (ER=2.64, adjusted P value<0.02) and in male patients compared with male controls (ER=3.43, P value<0.03). Expression of LINC-ROR was higher in total patients compared with total controls (ER=10.36, adjusted P value<0.0001) and in both male and female patients compared with sex-matched controls (ER=4.57, adjusted P value=0.03 and ER=23.47, adjusted P value=0.0019, respectively). Finally, expression of MEG3 was higher in total patients compared with total controls (ER=13.94, adjusted P value<0.0001) and in both male and female patients compared with sex-matched controls (ER=8.60, adjusted P value<0.004 and ER=22.58, adjusted P value<0.0085, respectively). ROC curve analysis revealed that MEG3 and LINC-ROR have diagnostic power of 0.77 and 0.73, respectively. Other lncRNAs had AUC values less than 0.7. Expression of none of lncRNAs was correlated with age of patients, disease duration, disease stage, MMSE or UPDRS. The current study provides further evidence for dysregulation of lncRNAs in the circulation of PD patients.
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Affiliation(s)
| | - Pooneh Gorji
- Men's Health and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mahdi Gholipour
- Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Bashdar Mahmud Hussen
- Department of Pharmacognosy, College of Pharmacy, Hawler Medical University, Erbil, Iraq
| | - Mehrdokht Mazdeh
- Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Solat Eslami
- Dietary Supplements and Probiotic Research Center, Alborz University of Medical Sciences, Karaj, Iran.,Department of Medical Biotechnology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran
| | - Mohammad Taheri
- Skull Base Research Center, Loghman Hakim Hospital, Shahid Behehsti University of Medical Sciences, Tehran, Iran.,Institute of Human Genetics, Jena University Hospital, Jena, Germany
| | - Soudeh Ghafouri-Fard
- Department of Medical Genetics, School of Medicine, Shahid Behehsti University of Medical Sciences, Tehran, Iran
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Gao X, Yang J, Wang D, Zeng Q, Li F, Zhou S, Zhang X, Fan C, Gao Z, Zhao Y. Association between HULC rs7763881 and cancer risk: an updated Meta-analysis. NUCLEOSIDES, NUCLEOTIDES & NUCLEIC ACIDS 2021; 41:85-96. [PMID: 34865614 DOI: 10.1080/15257770.2021.2008433] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Revised: 10/23/2021] [Accepted: 11/15/2021] [Indexed: 06/13/2023]
Abstract
In recent years, several case-control studies have explored the association between the rs7763881 locus polymorphism of the HULC gene and cancer risk, however, the findings have been inconsistent. Therefore, a meta-analysis was conducted to clarify the association. Relevant case-control studies were obtained from CNKI, Embase, Web of Science and PubMed databases. RevMan software was used to perform data analysis. A total of 8 case-control studies containing 4036 cases and 5286 controls were included in the current meta-analysis. The overall analysis results showed no significant association between the rs7763881 locus polymorphism and cancer risk. However, stratified analysis based on cancer type showed that the rs7763881 locus polymorphism was associated with the decreased risk of hepatocellular cancer, colorectal cancer and esophageal cancer. In conclusion, the current findings suggest that the rs7763881 polymorphic loci located on the HULC gene may serve as a biomarker for determining an individual's risk of hepatocellular cancer, colorectal cancer and esophageal cancer.
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Affiliation(s)
- Xueren Gao
- School of Pharmacy, Yancheng Teachers' University, Yancheng, China
| | - Jiaxin Yang
- School of Pharmacy, Yancheng Teachers' University, Yancheng, China
| | - Dongbo Wang
- School of Pharmacy, Yancheng Teachers' University, Yancheng, China
| | - Qinghang Zeng
- School of Pharmacy, Yancheng Teachers' University, Yancheng, China
| | - Fangting Li
- School of Pharmacy, Yancheng Teachers' University, Yancheng, China
| | - Sasha Zhou
- School of Pharmacy, Yancheng Teachers' University, Yancheng, China
| | - Xue Zhang
- School of Pharmacy, Yancheng Teachers' University, Yancheng, China
| | - Chen Fan
- School of Pharmacy, Yancheng Teachers' University, Yancheng, China
| | - Ziyan Gao
- School of Pharmacy, Yancheng Teachers' University, Yancheng, China
| | - Yining Zhao
- School of Pharmacy, Yancheng Teachers' University, Yancheng, China
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Li Y, Wang J, Wang F, Gao C, Cao Y, Wang J. Development and Verification of an Autophagy-Related lncRNA Signature to Predict Clinical Outcomes and Therapeutic Responses in Ovarian Cancer. Front Med (Lausanne) 2021; 8:715250. [PMID: 34671615 PMCID: PMC8521014 DOI: 10.3389/fmed.2021.715250] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Accepted: 08/30/2021] [Indexed: 12/13/2022] Open
Abstract
Objective: Long noncoding RNAs (lncRNAs) are key regulators during ovarian cancer initiation and progression and are involved in mediating autophagy. In this study, we aimed to develop a prognostic autophagy-related lncRNA signature for ovarian cancer. Methods: Autophagy-related abnormally expressed lncRNAs were screened in ovarian cancer with the criteria values of |correlation coefficient| > 0.4 and p < 0.001. Based on them, a prognostic lncRNA signature was established. The Kaplan–Meier overall survival analysis was conducted in high- and low-risk samples in the training, verification, and entire sets, followed by receiver operating characteristics (ROCs) of 7-year survival. Multivariate Cox regression analysis was used for assessing the predictive independency of this signature after adjusting other clinical features. The associations between the risk scores and immune cell infiltration, PD-L1 expression, and sensitivity of chemotherapy drugs were assessed in ovarian cancer. Results: A total of 66 autophagy-related abnormally expressed lncRNAs were identified in ovarian cancer. An autophagy-related lncRNA signature was constructed for ovarian cancer. High-risk scores were indicative of poorer prognosis compared with the low-risk scores in the training, verification, and entire sets. ROCs of 7-year survival confirmed the well-predictive efficacy of this model. Following multivariate Cox regression analysis, this model was an independent prognostic factor. There were distinct differences in infiltrations of immune cells, PD-L1 expression, and sensitivity of chemotherapy drugs between high- and low-risk samples. Conclusions: This study constructed an autophagy-related lncRNA signature that was capable of predicting clinical outcomes and also therapeutic responses for ovarian cancer.
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Affiliation(s)
- Yan Li
- Department of Obstetrics and Gynecology, The Yancheng Clinical College of Xuzhou Medical University, The First People's Hospital of Yancheng, Yancheng, China
| | - Juan Wang
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Fang Wang
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Chengzhen Gao
- Department of Obstetrics and Gynecology, The Yancheng Clinical College of Xuzhou Medical University, The First People's Hospital of Yancheng, Yancheng, China
| | - Yuanyuan Cao
- Department of Obstetrics and Gynecology, The Yancheng Clinical College of Xuzhou Medical University, The First People's Hospital of Yancheng, Yancheng, China
| | - Jianhua Wang
- Department of Gastroenterology, The Yancheng Clinical College of Xuzhou Medical University, The First People's Hospital of Yancheng, Yancheng, China
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31
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Sabol M, Calleja-Agius J, Di Fiore R, Suleiman S, Ozcan S, Ward MP, Ozretić P. (In)Distinctive Role of Long Non-Coding RNAs in Common and Rare Ovarian Cancers. Cancers (Basel) 2021; 13:5040. [PMID: 34680193 PMCID: PMC8534192 DOI: 10.3390/cancers13205040] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Revised: 10/04/2021] [Accepted: 10/06/2021] [Indexed: 02/05/2023] Open
Abstract
Rare ovarian cancers (ROCs) are OCs with an annual incidence of fewer than 6 cases per 100,000 women. They affect women of all ages, but due to their low incidence and the potential clinical inexperience in management, there can be a delay in diagnosis, leading to a poor prognosis. The underlying causes for these tumors are varied, but generally, the tumors arise due to alterations in gene/protein expression in cellular processes that regulate normal proliferation and its checkpoints. Dysregulation of the cellular processes that lead to cancer includes gene mutations, epimutations, non-coding RNA (ncRNA) regulation, posttranscriptional and posttranslational modifications. Long non-coding RNA (lncRNA) are defined as transcribed RNA molecules, more than 200 nucleotides in length which are not translated into proteins. They regulate gene expression through several mechanisms and therefore add another level of complexity to the regulatory mechanisms affecting tumor development. Since few studies have been performed on ROCs, in this review we summarize the mechanisms of action of lncRNA in OC, with an emphasis on ROCs.
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Affiliation(s)
- Maja Sabol
- Laboratory for Hereditary Cancer, Division of Molecular Medicine, Ruđer Bošković Institute, HR-10000 Zagreb, Croatia;
| | - Jean Calleja-Agius
- Department of Anatomy, Faculty of Medicine and Surgery, University of Malta, MSD 2080 Msida, Malta; (J.C.-A.); (R.D.F.); (S.S.)
| | - Riccardo Di Fiore
- Department of Anatomy, Faculty of Medicine and Surgery, University of Malta, MSD 2080 Msida, Malta; (J.C.-A.); (R.D.F.); (S.S.)
- Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA
| | - Sherif Suleiman
- Department of Anatomy, Faculty of Medicine and Surgery, University of Malta, MSD 2080 Msida, Malta; (J.C.-A.); (R.D.F.); (S.S.)
| | - Sureyya Ozcan
- Department of Chemistry, Middle East Technical University (METU), 06800 Ankara, Turkey;
- Cancer Systems Biology Laboratory (CanSyl), Middle East Technical University (METU), 06800 Ankara, Turkey
| | - Mark P. Ward
- Department of Histopathology, Trinity St James’s Cancer Institute, Emer Casey Molecular Pathology Laboratory, Trinity College Dublin and Coombe Women’s and Infants University Hospital, D08 RX0X Dublin, Ireland;
| | - Petar Ozretić
- Laboratory for Hereditary Cancer, Division of Molecular Medicine, Ruđer Bošković Institute, HR-10000 Zagreb, Croatia;
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Elevated LINC00909 Promotes Tumor Progression of Ovarian Cancer via Regulating the miR-23b-3p/MRC2 Axis. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2021; 2021:5574130. [PMID: 34336102 PMCID: PMC8318762 DOI: 10.1155/2021/5574130] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Revised: 04/11/2021] [Accepted: 06/05/2021] [Indexed: 01/05/2023]
Abstract
Ovarian cancer (OC), the third common gynecologic malignancy, contributes to the most cancer-caused mortality in women. However, 70% of patients with OC are diagnosed at an advanced stage, of which the 5-year survival is less than 30%. Long noncoding RNAs (long ncRNAs or lncRNA), a type of RNA with exceeding 200 nucleotides in length but no protein-coding capability, have been demonstrated to involve the pathogenesis of various cancers and show considerable potential in the diagnosis of OC. In this study, we found that the LINC00909 expression in tumor and serum specimens of OC patients was elevated, determined by real-time quantitative, and droplet digital PCR. In receiver operating characteristic (ROC) analysis, our results revealed that serum LINC00909 distinguished cancers from normal ovarian tissue with 87.8% of sensitivity and 69.6% of specificity (AUC, 81.2%) and distinguished serous ovarian cancer from normal ovarian tissue with 90.0% of sensitivity and 75.9% of specificity (AUC, 84.5%). Furthermore, we observed that the tumor and serum LINC00909 level was positively associated with the International Federation of Gynecology and Obstetrics (FIGO) stage and the Eastern Cooperative Oncology Group (ECOG) score (reflecting patients' performance status). Also, patients with low serum LINC00909 level showed a longer overall (hazard ratio, HR = 1.874, p = 0.0004) and progression-free (HR = 1.656, p = 0.0017) survival. Functional assays indicated that the elevation of LINC00909 expression contributes to cell proliferation, migration, and invasion capability of ovarian cancer cells. Besides, we demonstrated that LINC00909 functions as a competing endogenous RNA (ceRNA) of MRC2 mRNA by sponging miR-23-3p, and thereby promotes epithelial-to-mesenchymal transition (EMT) of ovarian cancer cells. Therefore, we highlight that the LINC00909/miR-23b-3p/MRC2 axis is implicated in the pathogenesis of ovarian cancer, and serum LINC00909 may be a promising biomarker for the diagnosis of OC.
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Zamaraev AV, Volik PI, Sukhikh GT, Kopeina GS, Zhivotovsky B. Long non-coding RNAs: A view to kill ovarian cancer. Biochim Biophys Acta Rev Cancer 2021; 1876:188584. [PMID: 34157315 DOI: 10.1016/j.bbcan.2021.188584] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 06/15/2021] [Accepted: 06/16/2021] [Indexed: 12/22/2022]
Abstract
An emerging role of long non-coding RNAs (lncRNAs) in tumor progression has been revealed in the last decade. Through interactions with nucleic acids and proteins, lncRNAs could act as enhancers, scaffolds or decoys for a number of oncoproteins and tumor suppressors. The aberrant lncRNA expression or mutations are often associated with changes in a variety of cellular processes, including proliferation, stress response and cell death. Here, we will focus on the tumor-associated lncRNAs in ovarian cancer according to their contribution to cancer hallmarks, such as intense proliferation, cell death resistance, altered energy metabolism, invasion and metastasis, and immune evasion. Moreover, the potential clinical implications of lncRNAs and their significance for the diagnosis, prognosis and therapy of ovarian cancer will be discussed.
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Affiliation(s)
- Alexey V Zamaraev
- Faculty of Medicine, MV Lomonosov Moscow State University, 119991 Moscow, Russia
| | - Pavel I Volik
- Faculty of Medicine, MV Lomonosov Moscow State University, 119991 Moscow, Russia
| | - Gennady T Sukhikh
- V. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, 117997 Moscow, Russia
| | - Gelina S Kopeina
- Faculty of Medicine, MV Lomonosov Moscow State University, 119991 Moscow, Russia.
| | - Boris Zhivotovsky
- Faculty of Medicine, MV Lomonosov Moscow State University, 119991 Moscow, Russia; Division of Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Box 210, 17177 Stockholm, Sweden.
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Zhao SP, Yu C, Yang MS, Liu ZL, Yang BC, Xiao XF. Long Non-coding RNA FENDRR Modulates Autophagy Through Epigenetic Suppression of ATG7 via Binding PRC2 in Acute Pancreatitis. Inflammation 2021; 44:999-1013. [PMID: 33417179 DOI: 10.1007/s10753-020-01395-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Revised: 11/19/2020] [Accepted: 12/07/2020] [Indexed: 11/30/2022]
Abstract
Acute pancreatitis (AP) is an inflammatory, complicated pancreatic disease, carrying significant morbidity and mortality. However, the molecular and cellular mechanisms involved in AP pathogenesis remain to be elucidated. Here, we explore the role of FOXF1 adjacent non-coding developmental regulatory RNA (FENDRR) in AP progression. Caerulein with or without LPS- induced or taurolithocholic acid 3-sulfate (TLC-S)-induced AP mouse models and cell models were performed for the validation of FENDRR expression in vivo and in vitro, respectively. Histopathological examinations of pancreatic tissues were performed to evaluate the severity of AP. Transmission electron microscopy was utilized to visualize the autophagic vacuoles. siRNA specifically targeting FENDRR was further applied. Flow cytometry was employed to assess cell apoptosis. ELISA, immunoflureoscence, and western blotting analysis were also performed to determine the levels of inflammatory cytokines and autophagy activity. RNA immunoprecipitation (RIP) and chromatin immunoprecipitation (ChIP) assays were carried out to reveal the epigenetic regulation of FENDRR on ATG7. Additionally, silencing FENDRR was also verified in AP mouse models. Higher FENDRR and impaired autophagy were displayed in both AP mouse models and cell models. FENDRR knockdown dramatically attenuated caerulein- or TLC-S-induced AR42J cells apoptosis and autophagy suppression. Further mechanistic experiments implied that the action of FENDRR is moderately attributable to its repression of ATG7 via direct interaction with the epigenetic repressor PRC2. Moreover, the silencing of FENDRR significantly induced the promotion of ATG7, thus alleviating the development of AP in vivo. Our study highlights FENDRR as a novel target that may contribute to AP progression, suggesting a therapeutic target for AP treatment.
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Affiliation(s)
- Shang-Ping Zhao
- The Third Xiangya Hospital of Central South University, No. 138, Tongzipo Road, Yuelu District, Changsha, 410013, Hunan Province, People's Republic of China
| | - Can Yu
- The Third Xiangya Hospital of Central South University, No. 138, Tongzipo Road, Yuelu District, Changsha, 410013, Hunan Province, People's Republic of China
| | - Ming-Shi Yang
- The Third Xiangya Hospital of Central South University, No. 138, Tongzipo Road, Yuelu District, Changsha, 410013, Hunan Province, People's Republic of China
| | - Zuo-Liang Liu
- The Third Xiangya Hospital of Central South University, No. 138, Tongzipo Road, Yuelu District, Changsha, 410013, Hunan Province, People's Republic of China
| | - Bing-Chang Yang
- The Third Xiangya Hospital of Central South University, No. 138, Tongzipo Road, Yuelu District, Changsha, 410013, Hunan Province, People's Republic of China
| | - Xue-Fei Xiao
- The Third Xiangya Hospital of Central South University, No. 138, Tongzipo Road, Yuelu District, Changsha, 410013, Hunan Province, People's Republic of China.
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Jin L, Hong N, Ai X, Wang J, Li Z, Han Z, Zhang Q, Yu Y, Sun K. LncRNAs as Therapeutic Targets for Autophagy-involved Cardiovascular Diseases: A Review of Molecular Mechanism and T herapy Strategy. Curr Med Chem 2021; 28:1796-1814. [PMID: 32196441 DOI: 10.2174/0929867327666200320161835] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2019] [Revised: 02/12/2020] [Accepted: 03/06/2020] [Indexed: 11/22/2022]
Abstract
BACKGROUND Cardiovascular diseases (CVDs) remain the leading cause of death worldwide. The concept of precision medicine in CVD therapy today requires the incorporation of individual genetic and environmental variability to achieve personalized disease prevention and tailored treatment. Autophagy, an evolutionarily conserved intracellular degradation process, has been demonstrated to be essential in the pathogenesis of various CVDs. Nonetheless, there have been no effective treatments for autophagy- involved CVDs. Long noncoding RNAs (lncRNAs) are noncoding RNA sequences that play versatile roles in autophagy regulation, but much needs to be explored about the relationship between lncRNAs and autophagy-involved CVDs. SUMMARY Increasing evidence has shown that lncRNAs contribute considerably to modulate autophagy in the context of CVDs. In this review, we first summarize the current knowledge of the role lncRNAs play in cardiovascular autophagy and autophagy-involved CVDs. Then, recent developments of antisense oligonucleotides (ASOs) designed to target lncRNAs to specifically modulate autophagy in diseased hearts and vessels are discussed, focusing primarily on structure-activity relationships of distinct chemical modifications and relevant clinical trials. PERSPECTIVE ASOs are promising in cardiovascular drug innovation. We hope that future studies of lncRNA-based therapies would overcome existing technical limitations and help people who suffer from autophagy-involved CVDs.
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Affiliation(s)
- Lihui Jin
- Department of Pediatric Cardiology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China
| | - Nanchao Hong
- Department of Pediatric Cardiology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China
| | - Xuefeng Ai
- Department of Pediatric Cardiothoracic Surgery, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
| | - Jing Wang
- Department of Pediatric Cardiology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China
| | - Zhuoyan Li
- Department of Pediatric Cardiology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China
| | - Zhenyuan Han
- Department of Oral Pathology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200001, China
| | - Qi Zhang
- Department of Pediatric Cardiology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China
| | - Yu Yu
- Department of Pediatric Cardiology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China
| | - Kun Sun
- Department of Pediatric Cardiology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China
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Miao W, Lu T, Liu X, Yin W, Zhang H. LncRNA SNHG8 induces ovarian carcinoma cells cellular process and stemness through Wnt/β-catenin pathway. Cancer Biomark 2021; 28:459-471. [PMID: 32538821 DOI: 10.3233/cbm-190640] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Ovarian carcinoma ranks fifth in the leading causes of cancer-relevant deaths among the female, with the highest fatality rate in all gynecological malignant tumors and the rising incidence worldwide. Mounting evidence has unveiled that lncRNAs are implicated in the tumorigenesis and cancer development. Several studies have proven the carcinogenic role of SNHG8 in various malignancies, but the physiological functions of SNHG8 in ovarian carcinoma need more detailed explanations. The present study certified that inhibition of SNHG8 executed suppressive activities in ovarian carcinoma by obstructing cell proliferation, migration, EMT process and stemness as well as driving cell apoptosis. Moreover, SNHG8 bound with CAPRIN1 and positively modulated the expression of CAPRIN1. Further experiments manifested that CTNNB1 and Axin1 displayed a binding affinity with CAPRIN1. Knockdown of CAPRIN1 promoted the mRNA degradation of CTNNB1 and Axin1. Finally, we corroborated that CTNNB1 (or Axin1) ectopic expression or activation of Wnt/β-catenin pathway abrogated the effects of SNHG8 downregulation on the cellular process of ovarian carcinoma cells. To summarize, SNHG8 acted as an oncogene in ovarian carcinoma via targeting Wnt/β-catenin pathway, providing a new insight into understanding ovarian carcinoma at the molecular level.
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Affiliation(s)
- Wei Miao
- Department of Health, Jining First People's Hospital, Jining, Shandong, China.,Department of Health, Jining First People's Hospital, Jining, Shandong, China
| | - Tanmin Lu
- Department of Gynecology and Obstetrics, Liaocheng People's Hospital, Liaocheng, Shandong, China.,Department of Health, Jining First People's Hospital, Jining, Shandong, China
| | - Xiaolin Liu
- Department of Gynecology and Obstetrics, Qilu Hospital of Shandong University, Ji'nan, Shandong, China
| | - Weiyang Yin
- Department of General surgery, Jining First People's Hospital, Jining, Shandong, China
| | - Hui Zhang
- Department of Gynecology and Obstetrics, Qilu Hospital of Shandong University, Ji'nan, Shandong, China
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β-Elemene suppresses tumor growth of diffuse large B-cell lymphoma through regulating lncRNA HULC-mediated apoptotic pathway. Biosci Rep 2021; 40:222028. [PMID: 32010942 PMCID: PMC7012654 DOI: 10.1042/bsr20190804] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2019] [Revised: 01/23/2020] [Accepted: 01/28/2020] [Indexed: 01/04/2023] Open
Abstract
Background: Diffuse large B-cell lymphoma (DLBCL) is considered the most common aggressive subtype of lymphoma. A number of DLBCL patients fail to achieve a response to currently available therapies or develop resistance. β-Elemene is derived from herb Curcuma wenyujin, and exhibits anti-tumor activity in both solid and non-solid tumors through modulating several molecular signaling pathways. We aimed to explore the role of β-elemene in DLBCL treatment and elucidate the involved mechanism. Materials and methods: Cell viability, apoptosis and expressions of related proteins were assessed and in vivo study were performed to determine the tumor suppressive effect of β-elemene and explore the molecular mechanisms. Results: β-Elemene significantly suppressed the viability of DLBCL cells, and β-elemene down-regulated the lncRNA HULC expression and regulated key pro-apoptotic and anti-apoptotic proteins to induce significant apoptosis of DLBCL cells. HULC overexpression could decrease the β-elemene induced apoptosis, while HULC knockdown increased the apoptosis in DLBCL cells. In vivo study further confirmed that β-elemene could suppress the growth of DLBCL xenograft and regulate the HULC expression and the critical proteins of the apoptotic pathway. Conclusion: β-Elemene performs as a tumor suppressor and modulator of HULC-mediated apoptotic pathway in DLBCL and will be an alternative candidate for clinical application.
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38
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Kong D, Long D, Liu B, Pei D, Cao N, Zhang G, Xia Z, Luo M. Downregulation of long non-coding RNA LOC101928477 correlates with tumor progression by regulating the epithelial-mesenchymal transition in esophageal squamous cell carcinoma. Thorac Cancer 2021; 12:1303-1311. [PMID: 33713583 PMCID: PMC8088935 DOI: 10.1111/1759-7714.13858] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Revised: 01/09/2021] [Accepted: 01/09/2021] [Indexed: 02/07/2023] Open
Abstract
Background Esophageal squamous cell carcinoma (ESCC) is one of the deadliest malignancies. There is a growing body of evidence showing that long non‐coding RNAs (lncRNAs) play critical roles in ESCC oncogenesis. The present study aimed to explore the role of LOC101928477, a newly discovered lncRNA, in the development and metastasis of ESCC. Methods In this study, real‐time PCR, western blotting, cell counting kit‐8 (CCK‐8), flow cytometry, colony formation, wound healing, transwell migration/invasion assay, immunofluorescence, and immunohistochemistry were used. We also applied an in situ xenograft mouse model and a lung metastasis mouse model to verify our findings. Results We determined that LOC101928477 expression was inhibited in ESCC tissue and ESCC cell lines when compared with controls. Moreover, forced expression of LOC101928477 effectively inhibited ESCC cell proliferation, colony formation, migration, and invasion via suppression of epithelial‐mesenchymal transition (EMT). Furthermore, LOC101928477 overexpression inhibited in situ tumor growth and lung metastasis in a mouse model. Conclusions Together, our results suggested that LOC101928477 could be a novel suppressor gene involved in ESCC progression.
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Affiliation(s)
- Demiao Kong
- Department of Thoracic Surgery, Guizhou Provincial People's Hospital, Guiyang, China
| | - Dali Long
- Department of Intensive Care Unit, Guizhou Provincial People's Hospital, Guiyang, China
| | - Bo Liu
- Department of Thoracic Surgery, Guizhou Provincial People's Hospital, Guiyang, China
| | - Dengke Pei
- Department of Thoracic Surgery, Guizhou Provincial People's Hospital, Guiyang, China
| | - Na Cao
- Department of Logistics, Guizhou Provincial People's Hospital, Guizhou, Guiyang, China
| | - Guihua Zhang
- Department of Thoracic Surgery, Guizhou Provincial People's Hospital, Guiyang, China
| | - Zhenkun Xia
- Department of Thoracic Surgery, Guizhou Provincial People's Hospital, Guiyang, China
| | - Meng Luo
- Department of Thoracic Surgery, Guizhou Provincial People's Hospital, Guiyang, China
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Klein MI, Cannataro VL, Townsend JP, Newman S, Stern DF, Zhao H. Identifying modules of cooperating cancer drivers. Mol Syst Biol 2021; 17:e9810. [PMID: 33769711 PMCID: PMC7995435 DOI: 10.15252/msb.20209810] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2020] [Revised: 01/20/2021] [Accepted: 01/26/2021] [Indexed: 12/22/2022] Open
Abstract
Identifying cooperating modules of driver alterations can provide insights into cancer etiology and advance the development of effective personalized treatments. We present Cancer Rule Set Optimization (CRSO) for inferring the combinations of alterations that cooperate to drive tumor formation in individual patients. Application to 19 TCGA cancer types revealed a mean of 11 core driver combinations per cancer, comprising 2-6 alterations per combination and accounting for a mean of 70% of samples per cancer type. CRSO is distinct from methods based on statistical co-occurrence, which we demonstrate is a suboptimal criterion for investigating driver cooperation. CRSO identified well-studied driver combinations that were not detected by other approaches and nominated novel combinations that correlate with clinical outcomes in multiple cancer types. Novel synergies were identified in NRAS-mutant melanomas that may be therapeutically relevant. Core driver combinations involving NFE2L2 mutations were identified in four cancer types, supporting the therapeutic potential of NRF2 pathway inhibition. CRSO is available at https://github.com/mikekleinsgit/CRSO/.
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Affiliation(s)
- Michael I Klein
- Program in Computational Biology and BioinformaticsYale UniversityNew HavenCTUSA
- Bioinformatics R&DSema4StamfordCTUSA
| | - Vincent L Cannataro
- Department of BiologyEmmanuel CollegeBostonMAUSA
- Department of BiostatisticsYale School of Public HealthNew HavenCTUSA
| | - Jeffrey P Townsend
- Program in Computational Biology and BioinformaticsYale UniversityNew HavenCTUSA
- Department of BiostatisticsYale School of Public HealthNew HavenCTUSA
- Yale Cancer CenterYale UniversityNew HavenCTUSA
| | | | - David F Stern
- Yale Cancer CenterYale UniversityNew HavenCTUSA
- Department of PathologyYale School of MedicineNew HavenCTUSA
| | - Hongyu Zhao
- Program in Computational Biology and BioinformaticsYale UniversityNew HavenCTUSA
- Department of BiostatisticsYale School of Public HealthNew HavenCTUSA
- Yale Cancer CenterYale UniversityNew HavenCTUSA
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Abdi E, Latifi-Navid S, Latifi-Navid H, Safaralizadeh R. LncRNA polymorphisms and upper gastrointestinal cancer risk. Pathol Res Pract 2021; 218:153324. [DOI: 10.1016/j.prp.2020.153324] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2020] [Revised: 12/13/2020] [Accepted: 12/15/2020] [Indexed: 02/07/2023]
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Wang JF, Wang Y, Zhang SW, Chen YY, Qiu Y, Duan SY, Li BP, Chen JQ. Expression and Prognostic Analysis of Integrins in Gastric Cancer. JOURNAL OF ONCOLOGY 2020; 2020:8862228. [PMID: 33335550 PMCID: PMC7722456 DOI: 10.1155/2020/8862228] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/14/2020] [Revised: 10/28/2020] [Accepted: 11/09/2020] [Indexed: 12/14/2022]
Abstract
BACKGROUND Integrins are involved in the biological process of a variety of cancers, but their importance in the diagnosis and prognosis of gastric cancer (GC) is still unclear. Therefore, this study aimed at exploring the significance of ITG gene expression in GC to evaluate its diagnosis and prognosis. METHODS GEPIA data were used to evaluate the mRNA expression of ITG genes in GC patients. The prognostic value of these genes was assessed by analyzing their mRNA expression using the Kaplan-Meier curve. The biological function of ITG genes was evaluated by GC tissue sequencing combined with GSEA bioinformatics. Based on the sequencing data, ITGA5 with the largest expression difference was selected for verification, and RT-PCR was used to verify its mRNA expression level in 40 pairs of GC and normal tissues. RESULTS ITG (A2, A3, A4, A5, A6, A11, AE, AL, AM, AV, AX, B1, B2, B4, B5, B6, and B8) was highly expressed in GC tissues, while ITGA8 was low, compared with their expression in normal tissues. RNA-seq data shows that ITG (A2, A5, A11, AV, and B1) expression was associated with poor prognosis and overall survival. In addition, combined with the results of GC tissue mRNA sequencing, it was further found that the differentially expressed genes in the ITGs genes. ITGA5 was highly expressed in GC tissues compared with its expression in normal tissues, as evaluated by qRT-PCR (P < 0.001) and ROC (P < 0.001, AUC (95% CI) = 0.747 (0.641-0.851)), and confirmed that ITGA5 expression was a potential diagnostic marker for GC. Bioinformatics analysis revealed that the signaling pathway involved in ITGA5 was mainly enriched in focal adhesion, ECM-receptor interaction, and PI3K-AKT and was mainly involved in biological processes such as cell adhesion, extracellular matrix, and cell migration. CONCLUSION This study suggested that ITGs were associated with the diagnosis and prognosis of GC and discovered the prognostic value and biological role of ITGA5 in GC. Thus, ITGA5 might be used as a potential diagnostic marker for GC.
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Affiliation(s)
- Jun-Fu Wang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Ye Wang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Si-Wen Zhang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Ye-Yang Chen
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Yue Qiu
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Shao-Yi Duan
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Bo-Pei Li
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Jun-Qiang Chen
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning 530021, Guangxi Zhuang Autonomous Region, China
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LncRNAs in Ovarian Cancer Progression, Metastasis, and Main Pathways: ceRNA and Alternative Mechanisms. Int J Mol Sci 2020; 21:ijms21228855. [PMID: 33238475 PMCID: PMC7700431 DOI: 10.3390/ijms21228855] [Citation(s) in RCA: 151] [Impact Index Per Article: 30.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Revised: 11/16/2020] [Accepted: 11/18/2020] [Indexed: 12/12/2022] Open
Abstract
Ovarian cancer (OvCa) develops asymptomatically until it reaches the advanced stages with metastasis, chemoresistance, and poor prognosis. Our review focuses on the analysis of regulatory long non-coding RNAs (lncRNAs) competing with protein-coding mRNAs for binding to miRNAs according to the model of competitive endogenous RNA (ceRNA) in OvCa. Analysis of publications showed that most lncRNAs acting as ceRNAs participate in OvCa progression: migration, invasion, epithelial-mesenchymal transition (EMT), and metastasis. More than 30 lncRNAs turned out to be predictors of survival and/or response to therapy in patients with OvCa. For a number of oncogenic (CCAT1, HOTAIR, NEAT1, and TUG1 among others) and some suppressive lncRNAs, several lncRNA/miRNA/mRNA axes were identified, which revealed various functions for each of them. Our review also considers examples of alternative mechanisms of actions for lncRNAs besides being ceRNAs, including binding directly to mRNA or protein, and some of them (DANCR, GAS5, MALAT1, and UCA1 among others) act by both mechanisms depending on the target protein. A systematic analysis based on the data from literature and Panther or KEGG (Kyoto Encyclopedia of Genes and Genomes) databases showed that a significant part of lncRNAs affects the key pathways involved in OvCa metastasis, EMT, and chemoresistance.
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Silva VR, Neves SP, Santos LDS, Dias RB, Bezerra DP. Challenges and Therapeutic Opportunities of Autophagy in Cancer Therapy. Cancers (Basel) 2020; 12:cancers12113461. [PMID: 33233671 PMCID: PMC7699739 DOI: 10.3390/cancers12113461] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2020] [Revised: 11/14/2020] [Accepted: 11/16/2020] [Indexed: 02/07/2023] Open
Abstract
Simple Summary Autophagy is a physiological process characterized by the degradation of the cell components through lysosomes due to stimuli/stress. In this study, we review the challenges and therapeutic opportunities that autophagy presents in the treatment of cancer. We discussed the results of several studies that evaluated autophagy as a therapeutic strategy in cancer, both through the modulation of therapeutic resistance and the death of cancer cells. Moreover, we discussed the role of autophagy in the biology of cancer stem cells and the inhibition of this process as a strategy to overcome resistance and progression of cancer stem cells. Abstract Autophagy is a physiological cellular process that is crucial for development and can occurs in response to nutrient deprivation or metabolic disorders. Interestingly, autophagy plays a dual role in cancer cells—while in some situations, it has a cytoprotective effect that causes chemotherapy resistance, in others, it has a cytotoxic effect in which some compounds induce autophagy-mediated cell death. In this review, we summarize strategies aimed at autophagy for the treatment of cancer, including studies of drugs that can modulate autophagy-mediated resistance, and/or drugs that cause autophagy-mediated cancer cell death. In addition, the role of autophagy in the biology of cancer stem cells has also been discussed.
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Liu PF, Farooqi AA, Peng SY, Yu TJ, Dahms HU, Lee CH, Tang JY, Wang SC, Shu CW, Chang HW. Regulatory effects of noncoding RNAs on the interplay of oxidative stress and autophagy in cancer malignancy and therapy. Semin Cancer Biol 2020; 83:269-282. [PMID: 33127466 DOI: 10.1016/j.semcancer.2020.10.009] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Revised: 10/15/2020] [Accepted: 10/18/2020] [Indexed: 12/15/2022]
Abstract
Noncoding RNAs (ncRNAs) regulation of various diseases including cancer has been extensively studied. Reactive oxidative species (ROS) elevated by oxidative stress are associated with cancer progression and drug resistance, while autophagy serves as an ROS scavenger in cancer cells. However, the regulatory effects of ncRNAs on autophagy and ROS in various cancer cells remains complex. Here, we explore how currently investigated ncRNAs, mainly miRNAs and lncRNAs, are involved in ROS production through modulating antioxidant genes. The regulatory effects of miRNAs and lncRNAs on autophagy-related (ATG) proteins to control autophagy activity in cancer cells are discussed. Moreover, differential expression of ncRNAs in tumor and normal tissues of cancer patients are further analyzed using The Cancer Genome Atlas (TCGA) database. This review hypothesizes links between ATG genes- or antioxidant genes-modulated ncRNAs and ROS production, which might result in tumorigenesis, malignancy, and cancer recurrence. A better understanding of the regulation of ROS and autophagy by ncRNAs might advance the use of ncRNAs as diagnostic and prognostic markers as well as therapeutic targets in cancer therapy.
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Affiliation(s)
- Pei-Feng Liu
- Department of Biomedical Science and Environmental Biology, PhD Program in Life Science, College of Life Science, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan; Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan.
| | - Ammad Ahmad Farooqi
- Department of Molecular Oncology, Institute of Biomedical and Genetic Engineering (IBGE), Islamabad, Pakistan.
| | - Sheng-Yao Peng
- Department of Biomedical Science and Environmental Biology, PhD Program in Life Science, College of Life Science, Kaohsiung Medical University, Kaohsiung, Taiwan.
| | - Tzu-Jung Yu
- Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung, Taiwan.
| | - Hans-Uwe Dahms
- Department of Biomedical Science and Environmental Biology, PhD Program in Life Science, College of Life Science, Kaohsiung Medical University, Kaohsiung, Taiwan; Research Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 80424, Taiwan.
| | - Cheng-Hsin Lee
- Department of Biomedical Science and Environmental Biology, PhD Program in Life Science, College of Life Science, Kaohsiung Medical University, Kaohsiung, Taiwan.
| | - Jen-Yang Tang
- Department of Radiation Oncology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Radiation Oncology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
| | - Sheng-Chieh Wang
- Department of Biomedical Science and Environmental Biology, PhD Program in Life Science, College of Life Science, Kaohsiung Medical University, Kaohsiung, Taiwan.
| | - Chih-Wen Shu
- Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan; Institute of Biopharmaceutical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan.
| | - Hsueh-Wei Chang
- Department of Biomedical Science and Environmental Biology, PhD Program in Life Science, College of Life Science, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan; Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
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Wei J, Ge X, Tang Y, Qian Y, Lu W, Jiang K, Fang Y, Hwang M, Fu D, Xiao Q, Ding K. An Autophagy-Related Long Noncoding RNA Signature Contributes to Poor Prognosis in Colorectal Cancer. JOURNAL OF ONCOLOGY 2020; 2020:4728947. [PMID: 33149738 PMCID: PMC7603611 DOI: 10.1155/2020/4728947] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Revised: 09/21/2020] [Accepted: 09/29/2020] [Indexed: 12/23/2022]
Abstract
PURPOSE Colorectal cancer is one of the most common malignant primary tumors, prone to metastasis, and associated with a poor prognosis. As autophagy is closely related to the development and treatment of colorectal cancer, we investigated the potential prognostic value of long noncoding RNA (lncRNA) associated with autophagy in colorectal cancer. METHODS In this study, we acquired information on the expression of lncRNAs in colorectal cancer from the Cancer Genome Atlas (TCGA) database and found that 860 lncRNAs were associated with autophagy-related genes. Subsequently, univariate Cox regression analysis was used to investigate 32 autophagy-related lncRNAs linked to colon cancer prognosis. Subsequently, eight of the 32 autophagy-related lncRNAs (i.e., long intergenic nonprotein coding RNA 1503 [LINC01503], ZEB1 antisense RNA 1 [ZEB1-AS1], AC087481.3, AC008760.1, AC073896.3, AL138756.1, AL022323.1, and TNFRSF10A-AS1) were selected through multivariate Cox regression analysis. Based on these autophagy-related lncRNAs, a risk signature was constructed, and the patients were divided into high- and low-risk groups. RESULTS The high-risk group's overall survival time was significantly shorter than that of the low-risk group (p < 0.0001). Receiver operating characteristic curve analysis was performed to further confirm the validity of the model (area under the curve: 0.689). Moreover, multivariate regression suggested that the risk score was a significant prognostic risk factor in colorectal cancer. Gene set enrichment analysis showed that these gene sets are significantly enriched in cancer-related pathways, such as Kirsten rat sarcoma viral oncogene homolog (KRAS) signaling. CONCLUSION The risk signature of eight autophagy-related lncRNAs has prognostic potential for colorectal cancer. These autophagy-related lncRNAs may play a vital role in the biology of colorectal cancer.
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Affiliation(s)
- Jingsun Wei
- Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Xiaoxu Ge
- Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Yang Tang
- Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Yucheng Qian
- Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Wei Lu
- Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Kai Jiang
- Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Yimin Fang
- Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Maxwell Hwang
- Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Dongliang Fu
- Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Qian Xiao
- Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Kefeng Ding
- Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
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Yan C, Wei S, Han D, Wu L, Tan L, Wang H, Dong Y, Hua J, Yang W. LncRNA HULC shRNA disinhibits miR-377-5p to suppress the growth and invasion of hepatocellular carcinoma in vitro and hepatocarcinogenesis in vivo. ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:1294. [PMID: 33209874 PMCID: PMC7661872 DOI: 10.21037/atm-20-5556] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Background Aberrant expression of up-regulated long non-coding RNA [LncRNA highly upregulated in liver cancer (HULC)] has been observed to play an important regulatory role in the development of multiple human diseases. However, the molecular mechanism underlying the role of HULC and miR-377-5p in HCC needs to be urgently explored. Methods The mRNA and protein expression levels of HULC were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot in hepatocellular carcinoma (HCC) cell line HB611, HepG2 and H22, respectively. HULC-shRNA was transfected into HepG-2 cells, which were randomly divided into the control, shRNA-NC, and sh-HULC groups. The correlation between HULC and miR-377-5p was analyzed by performing a luciferase reporter assay. The targeting relationship between miR-377-5p and hypoxia-inhibitory factor-1α (HIF-1α) was also investigated using a luciferase reporter assay. Sh-HULC and miR-377-5p inhibitors were transfected either alone or together into HepG2 cells, and which were divided into the control group, the sh-HULC group, the miR-377-5p inhibitor, and the sh-HULC + inhibitor group for subsequent experiments. HepG2 cell proliferation and invasion were measured by 5-Ethynyl-2-Deoxyuridine (EdU) staining and Transwell invasion assay, respectively. Western plot was carried out to detect the protein expression levels of Ki67, PCNA, E-cadherin, and N-cadherin. Tumor xenograft mouse models were established to confirm the effect of HULC down-regulation on the development of HCC in vivo. Results The mRNA and protein expression levels of HULC were markedly increased, whereas the mRNA expression levels of miR-377-5p were decreased in HCC cell lines. HepG2 cell proliferation and invasion were suppressed in the Sh-HULC group, while miR-377-5p showed the opposite. Further experiments exhibited that miR-377-5p was targeted by HULC, and an negative correlation between HULC and miR-377-5p was observed. Importantly, the in vivo experiments indicated that down-regulation of HULC could inhibit tumor growth. Taken together, our research demonstrated that down-regulation of HULC plays an anti-cancer role through restrainingHepG2 cell proliferation and invasion. Conclusions In summary, our in vitro and in vivo findings confirmed HULC to play a role in the progression of HCC, with the underlying mechanism possibly involving the miR-377-5p/HIF-1α pathway.
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Affiliation(s)
- Chunxiao Yan
- Department of Gastroenterology, The First Affiliated Hospital of Henan University, Kaifeng, China
| | - Shutang Wei
- Department of Gastroenterology, The First Affiliated Hospital of Henan University, Kaifeng, China
| | - Dazheng Han
- Department of Gastroenterology, The First Affiliated Hospital of Henan University, Kaifeng, China
| | - Liping Wu
- Department of Gastroenterology, The First Affiliated Hospital of Henan University, Kaifeng, China
| | - Lixia Tan
- Department of Gastroenterology, The First Affiliated Hospital of Henan University, Kaifeng, China
| | - Hangyu Wang
- Department of Gastroenterology, The First Affiliated Hospital of Henan University, Kaifeng, China
| | - Yong Dong
- Department of Gastroenterology, The First Affiliated Hospital of Henan University, Kaifeng, China
| | - Jing Hua
- Department of Gastroenterology, The First Affiliated Hospital of Henan University, Kaifeng, China
| | - Wenyi Yang
- Department of Gastroenterology, The First Affiliated Hospital of Henan University, Kaifeng, China
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He J, Yang T, He W, Jiang S, Zhong D, Xu Z, Wei Q, Zhang Y, Shi C. Liver X receptor inhibits the growth of hepatocellular carcinoma cells via regulating HULC/miR-134-5p/FOXM1 axis. Cell Signal 2020; 74:109720. [DOI: 10.1016/j.cellsig.2020.109720] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2020] [Revised: 07/16/2020] [Accepted: 07/17/2020] [Indexed: 12/12/2022]
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Yang Z, Li G, Ding C, Sun W, Zhang J. Long non-coding RNA HULC exerts oncogenic activity on papillary thyroid cancer in vitro and in vivo. ARTIFICIAL CELLS NANOMEDICINE AND BIOTECHNOLOGY 2020; 48:326-335. [PMID: 31878795 DOI: 10.1080/21691401.2019.1703730] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Thyroid cancer is a frequently happened malignancy in human endocrine system. Papillary thyroid cancer (PTC) presents 70-80% of all thyroid cancer cases. Herein, we probed the possible oncogenic function of long non-coding RNA (lncRNA) highly up-regulated in liver cancer (HULC) in PTC. First, the HULC and microRNA-106a (miR-106a) expressions in PTC tissues and cells were tested. Plasmids or miRNAs transfections were done for altering HULC and miR-106a expressions. Then, cells viability and apoptosis, along with cell proliferative, migratory and invasive abilities, were tested, respectively. The PI3K/AKT and Wnt/β-catenin pathways activities were measured. Finally, the animal model of PTC was constructed and the tumour volumes and weights were gauged. We discovered that HULC and miR-106a had relative high expression levels in PTC tissues and cells. HULC overexpression enhanced TPC-1 cells viability and cell proliferative, migratory and invasive abilities. Silencing HULC induced TPC-1 cell apoptosis. miR-106a engaged in the oncogenic impacts of HULC. Moreover, HULC overexpression boosted PI3K/AKT and Wnt/β-catenin pathways activities via raising miR-106a expression. Besides, HULC overexpression enhanced the volumes and weights of PTC tumours. To sum up, HULC exhibited oncogenic function on PTC in vitro and in vivo.
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Affiliation(s)
- Zhijia Yang
- Department of Trauma Emergency, Huaihe Hospital, Henan University, Kaifeng, China
| | - Guoqing Li
- Department of Thyroid Surgery, Henan Provincial People's Hospital, Zhengzhou University, Zhengzhou, Henan, China
| | - Chao Ding
- Department of Thyroid Surgery, Henan Provincial People's Hospital, Zhengzhou University, Zhengzhou, Henan, China
| | - Wencong Sun
- Department of Thyroid Surgery, Henan Provincial People's Hospital, Zhengzhou University, Zhengzhou, Henan, China
| | - Ji Zhang
- Department of Thyroid Surgery, Henan Provincial People's Hospital, Zhengzhou University, Zhengzhou, Henan, China
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Qin Y, Sun W, Wang Z, Dong W, He L, Zhang T, Shao L, Zhang H. ATF2-Induced lncRNA GAS8-AS1 Promotes Autophagy of Thyroid Cancer Cells by Targeting the miR-187-3p/ATG5 and miR-1343-3p/ATG7 Axes. MOLECULAR THERAPY-NUCLEIC ACIDS 2020; 22:584-600. [PMID: 33230459 PMCID: PMC7562962 DOI: 10.1016/j.omtn.2020.09.022] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/26/2020] [Accepted: 09/17/2020] [Indexed: 02/07/2023]
Abstract
Long non-coding RNAs (lncRNAs) play an essential regulatory role in multiple cancers. However, the role of lncRNAs in papillary thyroid carcinoma (PTC) is still unknown. Here, GAS8-AS1, a novel lncRNA that is significantly downregulated in PTC, was selected for further investigation. The roles of GAS8-AS1 in PTC cells were verified by gain- and loss-of-function experiments. The functional mechanism of GAS8-AS1 on the microRNA (miR)-187-3p/ATG5 axis and miR-1343-3p/ATG7 axis in PTC cells was evaluated using bioinformatics analysis, luciferase reporter assay, Cell Counting Kit-8 (CCK-8) assay, immunohistochemistry analysis, transmission electron microscopy, and immunofluorescence. We found that GAS8-AS1 was downregulated in PTC tissues and cell lines. In patients with PTC, low GAS8-AS1 expression was associated with higher tumor-node-metastasis (TNM) stage and lymph node metastasis (LNM). Functionally, GAS8-AS1 significantly promoted autophagy and inhibited PTC cell proliferation in vitro and promoted tumorigenesis in vivo. Mechanistically, GAS8-AS1 acted as a sponge of miR-187-3p and miR-1343-3p and upregulated ATG5 and ATG7 expression, respectively. The transcription factor ATF2 regulated GAS8-AS1 by binding to the GAS8-AS1 promoter. In conclusion, upregulation of ATF2 activated GAS8-AS1-promoted autophagy of PTC cells by sponging oncogenic miR-187-3p and miR-1343-3p and upregulating the expression of ATG5 and ATG7, respectively, making GAS8-AS1 a potential prognostic biomarker and therapeutic target for PTC.
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Affiliation(s)
- Yuan Qin
- Department of Thyroid Surgery, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P. R. China
| | - Wei Sun
- Department of Thyroid Surgery, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P. R. China
| | - Zhihong Wang
- Department of Thyroid Surgery, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P. R. China
| | - Wenwu Dong
- Department of Thyroid Surgery, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P. R. China
| | - Liang He
- Department of Thyroid Surgery, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P. R. China
| | - Ting Zhang
- Department of Thyroid Surgery, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P. R. China
| | - Liang Shao
- Department of Thyroid Surgery, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P. R. China
| | - Hao Zhang
- Department of Thyroid Surgery, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P. R. China
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Yeganeh Z, Nabi M, Solymani S, Yazdian S, Razavinia A, Khalili A. The role of long-range non-coding RNAs NeST, NTT, BACE1-AS, CCAT2, FOXCUT and HULC as predictor biomarkers in breast cancer. GENE REPORTS 2020. [DOI: 10.1016/j.genrep.2020.100687] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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