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1
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Wang B, Zhou Q, Cheng CE, Gu YJ, Jiang TW, Qiu JM, Wei GN, Feng YD, Ren LH, Shi RH. Long noncoding RNA SNHG5 promotes 5-fluorouracil resistance in colorectal cancer by regulating miR-26b/p-glycoprotein axis. World J Gastrointest Oncol 2025; 17:102417. [DOI: 10.4251/wjgo.v17.i5.102417] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2024] [Revised: 02/03/2025] [Accepted: 02/27/2025] [Indexed: 05/15/2025] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is the second most prevalent cause of cancer-related mortality and is increasing in younger individuals. Chemotherapy, a crucial adjuvant systemic therapy for CRC management, often leads to resistance through poorly characterized underlying molecular mechanisms. The long noncoding RNA SNHG5 is highly expressed in CRC and promotes tumor proliferation and invasion, prompting us to hypothesize that SNHG5 may play a crucial role in the chemotherapeutic agent 5-fluorouracil (5-Fu) resistance in CRC.
AIM To identify the function and mechanism of SNHG5 in 5-Fu resistance in CRC.
METHODS Quantitative real-time polymerase chain reaction was performed to examine the expression of SNHG5 in CRC tissues from 22 5-Fu-sensitive patients and 14 5-Fu-resistant patients and in CRC cells and 5-Fu-resistant CRC cells. Cell viability and apoptosis were assessed in SNHG5-overexpressing CRC cells and SNHG5-knockdown 5-Fu-resistant CRC cells. SNHG5 function in 5-Fu resistance in CRC was further analyzed using a xenograft mouse model. SNHG5 interactions with microRNAs were predicted by bioinformatics analysis. Luciferase reporter and RNA immunoprecipitation assays were performed to verify the binding between SNHG5 and miR-26b. Rescue experiments were performed to validate the functional interaction between SNHG5 and the miR-26b/p-glycoprotein (Pgp) axis.
RESULTS SNHG5 expression was upregulated in 5-Fu-resistant CRC tissues and 5-Fu-resistant CRC cells. In vitro functional experiments demonstrated that SNHG5 overexpression significantly reduced cell apoptosis and enhanced cell viability, whereas SNHG5 knockdown in 5-Fu-resistant CRC cells increased cell apoptosis and decreased cell viability upon 5-Fu treatment. In a xenograft mouse model, we confirmed that SNHG5 overexpression led to a reduction in 5-Fu sensitivity in CRC in vivo. Mechanistically, SNHG5 acted as a molecular sponge for miR-26b. Rescue experiments validated that SNHG5 conferred 5-Fu resistance in CRC by regulating the miR-26b/Pgp axis.
CONCLUSION SNHG5/miR-26b/Pgp regulates CRC chemosensitivity, providing potential therapeutic targets for the treatment of 5-Fu-resistant CRC.
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Affiliation(s)
- Bin Wang
- School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
- Department of Gastroenterology, The Affiliated Changshu Hospital of Nantong University, Changshu No. 2 People’s Hospital, Suzhou 215500, Jiangsu Province, China
| | - Qian Zhou
- Department of Gastroenterology, The Affiliated Changshu Hospital of Nantong University, Changshu No. 2 People’s Hospital, Suzhou 215500, Jiangsu Province, China
| | - Cui-E Cheng
- Department of Gastroenterology, The Affiliated Changshu Hospital of Nantong University, Changshu No. 2 People’s Hospital, Suzhou 215500, Jiangsu Province, China
| | - Yi-Jie Gu
- Department of Gastroenterology, The Affiliated Changshu Hospital of Nantong University, Changshu No. 2 People’s Hospital, Suzhou 215500, Jiangsu Province, China
| | - Ting-Wang Jiang
- Department of Key Laboratory, The Affiliated Changshu Hospital of Nantong University, Changshu No. 2 People’s Hospital, Suzhou 215500, Jiangsu Province, China
| | - Jia-Ming Qiu
- Department of Pathology, The Affiliated Changshu Hospital of Nantong University, Changshu No. 2 People’s Hospital, Suzhou 215500, Jiangsu Province, China
| | - Gui-Ning Wei
- Department of Pharmacology, Guangxi Institute of Chinese Medicine and Pharmaceutical Science, Nanning 530022, Guangxi Zhuang Autonomous Region, China
| | - Ya-Dong Feng
- School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
- Department of Gastroenterology, Zhongda Hospital, Southeast University, Nanjing 210009, Jiangsu Province, China
| | - Li-Hua Ren
- School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
- Department of Gastroenterology, Zhongda Hospital, Southeast University, Nanjing 210009, Jiangsu Province, China
| | - Rui-Hua Shi
- School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
- Department of Gastroenterology, Zhongda Hospital, Southeast University, Nanjing 210009, Jiangsu Province, China
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Huang S, Ji P, Xu P, Liu K, Ge H, Yan Z, Cheng Q, Lv J, Zhang D. PLAGL2-STAU1-NCOA4 axis enhances gastric cancer peritoneal metastasis by resisting ferroptosis via ferritinophagy. Apoptosis 2025; 30:1058-1075. [PMID: 39987411 DOI: 10.1007/s10495-025-02083-3] [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] [Accepted: 01/24/2025] [Indexed: 02/24/2025]
Abstract
Peritoneal metastasis (PM) is the primary site of distant metastasis in gastric cancer (GC) and is associated with an advanced disease stage and poor prognosis. Due to its high resistance to chemotherapy, disseminated peritoneal lesions are often untreatable. A primary reason for therapy resistance in cancer cells is often their defective cell death execution mechanisms. Ferroptosis, a newly identified type of regulated cell death, is strongly linked to the emergence and formation of tumors. Earlier studies have demonstrated the significant role of RNA-binding proteins in ferroptosis. Nevertheless, the fundamental process linking Staufen Double-Stranded RNA Binding Protein 1 (STAU1) to ferroptosis in the peritoneal metastasis of gastric cancer is yet to be clarified. This study shows that the RNA-binding protein STAU1 is crucial for regulating ferroptosis in gastric cancer cells. Elevated levels of STAU1 are linked to unfavorable outcomes in individuals diagnosed with gastric cancer. STAU1 was up-regulated by PLAGL2 and decreased the stability of NCOA4 mRNA by binding to the 3'-untranslated region. Decreased NCOA4 expression inhibits the accumulation of reactive iron, the occurrence of the Fenton reaction, and cellular ROS generation in the GC cells. Additionally, we showed that NCOA4 is crucial in the process of ferritinophagy triggered by the reduction of STAU1 in gastric cancer cells. Ultimately, the process safeguards GC cells from ferroptosis. These findings elucidate the function of PLAGL2/STAU1/NCOA4 in the ferroptosis of gastric cancer cells and provide theoretical backing for possible diagnostic markers and treatment targets for peritoneal metastasis in gastric cancer.
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Affiliation(s)
- Shansong Huang
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Peicheng Ji
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Peng Xu
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Kanghui Liu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China
| | - Han Ge
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Zhengyuan Yan
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
- Department of Surgery, Nanjing Lishui People's Hospital, Nanjing, 211200, China
| | - Quan Cheng
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Jialun Lv
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Diancai Zhang
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
- Department of General Surgery, The Affiliated Suqian First People's Hospital of Nanjing Medical University, Suqian, Jiangsu Province, China.
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Gugnoni M, Kashyap MK, Wary KK, Ciarrocchi A. lncRNAs: the unexpected link between protein synthesis and cancer adaptation. Mol Cancer 2025; 24:38. [PMID: 39891197 PMCID: PMC11783725 DOI: 10.1186/s12943-025-02236-7] [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: 11/19/2024] [Accepted: 01/15/2025] [Indexed: 02/03/2025] Open
Abstract
Cancer progression relies on the ability of cells to adapt to challenging environments overcoming stresses and growth constraints. Such adaptation is a multifactorial process that depends on the rapid reorganization of many basic cellular mechanisms. Protein synthesis is often dysregulated in cancer, and translational reprogramming is emerging as a driving force of cancer adaptive plasticity. Long non-coding RNAs (lncRNAs) represent the main product of genome transcription. They outnumber mRNAs by an order of magnitude and their expression is regulated in an extremely specific manner depending on context, space and time. This heterogeneity is functional and allows lncRNAs to act as context-specific, fine-tuning controllers of gene expression. Multiple recent evidence underlines how, besides their consolidated role in transcription, lncRNAs are major players in translation control. Their capacity to establish multiple and highly dynamic interactions with proteins and other transcripts makes these molecules able to play a central role across all phases of protein synthesis. Even if through a myriad of different mechanisms, the action of these transcripts is dual. On one hand, by modulating the overall translation speed, lncRNAs participate in the process of metabolic adaptation of cancer cells under stress conditions. On the other hand, by prioritizing the synthesis of specific transcripts they help cancer cells to maintain high levels of essential oncogenes. In this review, we aim to discuss the most relevant evidence regarding the involvement of lncRNAs in translation regulation and to discuss how this specific function may affect cancer plasticity and resistance to stress. We also expect to provide one of the first collective perspectives on the way these transcripts modulate gene expression beyond transcription.
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Affiliation(s)
- Mila Gugnoni
- Laboratory of Translational Research, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy
| | - Manoj Kumar Kashyap
- Molecular Oncology Laboratory, Amity Stem Cell Institute, Amity Medical School, Amity University Haryana, Panchgaon (Manesar), Gurugram, Haryana, India.
| | - Kishore K Wary
- Department of Pharmacology and Regenerative Medicine, University of Illinois, Chicago, IL, USA.
| | - Alessia Ciarrocchi
- Laboratory of Translational Research, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy.
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Frolov A, D'sa E, Henderson C, Guzman MA, Hayat G, Martin JR. Complex Genetic Framework in Familial Amyotrophic Lateral Sclerosis With a C9ORF72 Mutation: A Case Report. Cureus 2024; 16:e76027. [PMID: 39835009 PMCID: PMC11743604 DOI: 10.7759/cureus.76027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/19/2024] [Indexed: 01/22/2025] Open
Abstract
A significantly diverse clinical presentation of amyotrophic lateral sclerosis (ALS), even in its best-studied familial form, continues to hinder current efforts to develop effective disease-modifying drugs for the cure of this rapidly progressive, fatal neuromuscular disease. We have previously shown that clinical heterogeneity of sporadic ALS (sALS) could be explained, at least in part, by its polygenic nature as well as by the presence of mutated genes linked to non-ALS neurological diseases and genes known to mediate ALS-related pathologies. We hypothesized that a similar genetic framework could also be present in patients with familial ALS (fALS). To test this hypothesis, we conducted post-mortem genetic screening of an individual with fALS and a mutation in the C9ORF72 gene. C9ORF72 mutations are highly penetrant and are present in the majority of fALS patients. Genetic screening by whole exome sequencing (WES) on the next generation sequencing (NGS) Illumina platform (San Diego, CA, USA) followed by examination of the respective rare (minor allele frequency (MAF) ≤ 0.01) pathological/deleterious genetic variants yielded results consistent with our hypothesis of the presence of a complex genetic framework in fALS. Additional members of this genetic framework were identified when the low-frequency (0.01 < MAF < 0.05) pathological/deleterious genetic variants were analyzed with the low-frequency biallelic AHNAK2, GLI3, PTIRM1, and ZNF254 variants, warranting a closer look at their potentially important role in fALS as C9ORF72 genetic modifiers as well as their link to both neuromuscular disorders/ALS and cancer. Therefore, in addition to the current genetic screening using a standard panel of ALS-related genes, a supplementary screening by WES could be very beneficial for the development of personalized treatment of ALS patients as well as in search of the respective efficient disease-modifying drugs.
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Affiliation(s)
- Andrey Frolov
- Department of Surgery - Center for Anatomical Science and Education, Saint Louis University School of Medicine, St. Louis, USA
| | - Elizabeth D'sa
- Department of Surgery - Center for Anatomical Science and Education, Saint Louis University School of Medicine, St. Louis, USA
| | - Camille Henderson
- Department of Surgery - Center for Anatomical Science and Education, Saint Louis University School of Medicine, St. Louis, USA
| | - Miguel A Guzman
- Department of Pathology, Saint Louis University School of Medicine, St. Louis, USA
| | - Ghazala Hayat
- Department of Neurology, Saint Louis University School of Medicine, St. Louis, USA
| | - John R Martin
- Department of Surgery - Center for Anatomical Science and Education, Saint Louis University School of Medicine, St. Louis, USA
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5
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Feng J, Tan A, Li W, Zheng Y. Small nucleolar RNA host gene 5 plays a role in orthodontic tooth movement by inhibiting osteoclast differentiation. Orthod Craniofac Res 2024; 27:775-784. [PMID: 38712649 DOI: 10.1111/ocr.12794] [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: 02/01/2024] [Revised: 04/01/2024] [Accepted: 04/09/2024] [Indexed: 05/08/2024]
Abstract
BACKGROUND AND OBJECTIVES The alveolar bone remodelling promoted by reasonable mechanical force triggers orthodontic tooth movement (OTM). The generation of osteoclasts is essential in this process. However, the mechanism of mechanical force mediating osteoclast differentiation remains elusive. Small nucleolar RNA host gene 5 (SNHG5), which was reported to mediate the osteogenic differentiation of bone marrow mesenchymal stem cells in our previous study, was downregulated in human periodontal ligament cells (hPDLCs) under mechanical force. At the same time, the RANKL/OPG ratio increased. Based on this, we probed into the role of SNHG5 in osteoclast formation during OTM and the relevant mechanism. MATERIALS AND METHODS SNHG5 and the RANKL/OPG ratio under different compressive forces were detected by western blotting (WB) and qRT-PCR. Impact of overexpression or knockdown of SNHG5 on osteoclast differentiation was detected by qRT-PCR, WB and transwell experiments. The combination of SNHG5 and C/EBPβ was verified by RNA immunoprecipitation and RNA pull-down assays. The expression of SNHG5 and osteoclast markers in gingiva were analysed by qRT-PCR and the paraffin sections of periodontal tissues were used for histological analysis. RESULTS Compressive force downregulated SNHG5 and upregulated the RANKL/OPG ratio in hPDLCs. Overexpression of SNHG5 inhibited RANKL's expression and osteoclast differentiation. SNHG5 combined with C/EBPβ, a regulator of osteoclast. The expression of SNHG5 in periodontal tissue decreased during OTM. CONCLUSION SNHG5 inhibited osteoclast differentiation during OTM, achieved by affecting RANKL secretion, which may provide a new idea to interfere with bone resorption during orthodontic treatment.
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Affiliation(s)
- Jingjing Feng
- Department of Orthodontics, National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Peking University School and Hospital of Stomatology, Beijing, PR China
| | - Anqi Tan
- Department of Orthodontics, National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Peking University School and Hospital of Stomatology, Beijing, PR China
| | - Weiran Li
- Department of Orthodontics, National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Peking University School and Hospital of Stomatology, Beijing, PR China
| | - Yunfei Zheng
- Department of Orthodontics, National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Peking University School and Hospital of Stomatology, Beijing, PR China
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6
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Liu X, Chen Y, Li Y, Bai J, Zeng Z, Wang M, Dong Y, Zhou Y. STAU1-mediated CNBP mRNA degradation by LINC00665 alters stem cell characteristics in ovarian cancer. Biol Direct 2024; 19:59. [PMID: 39080743 PMCID: PMC11288052 DOI: 10.1186/s13062-024-00506-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Accepted: 07/22/2024] [Indexed: 08/03/2024] Open
Abstract
BACKGROUND To investigate the role of lncRNA LINC00665 in modulating ovarian cancer stemness and its influence on treatment resistance and cancer development. METHODS We isolated ovarian cancer stem cells (OCSCs) from the COC1 cell line using a combination of chemotherapeutic agents and growth factors, and verified their stemness through western blotting and immunofluorescence for stem cell markers. Employing bioinformatics, we identified lncRNAs associated with ovarian cancer, with a focus on LINC00665 and its interaction with the CNBP mRNA. In situ hybridization, immunohistochemistry, and qPCR were utilized to examine their expression and localization, alongside functional assays to determine the effects of LINC00665 on CNBP. RESULTS LINC00665 employs its Alu elements to interact with the 3'-UTR of CNBP mRNA, targeting it for degradation. This molecular crosstalk enhances stemness by promoting the STAU1-mediated decay of CNBP mRNA, thereby modulating the Wnt and Notch signaling cascades that are pivotal for maintaining CSC characteristics and driving tumor progression. These mechanistic insights were corroborated by a series of in vitro assays and validated in vivo using tumor xenograft models. Furthermore, we established a positive correlation between elevated CNBP levels and increased disease-free survival in patients with ovarian cancer, underscoring the prognostic value of CNBP in this context. CONCLUSIONS lncRNA LINC00665 enhances stemness in ovarian cancer by mediating the degradation of CNBP mRNA, thereby identifying LINC00665 as a potential therapeutic target to counteract drug resistance and tumor recurrence associated with CSCs.
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Affiliation(s)
- Xiaofang Liu
- Department of Anus and Intestine Surgery, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, People's Republic of China
| | - Yang Chen
- Department of General Surgery, The First Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, People's Republic of China
| | - Ying Li
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, No. 36, Sanhao Street, Shenyang, Liaoning, 110004, People's Republic of China
| | - Jinling Bai
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, No. 36, Sanhao Street, Shenyang, Liaoning, 110004, People's Republic of China
| | - Zhi Zeng
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, No. 36, Sanhao Street, Shenyang, Liaoning, 110004, People's Republic of China
| | - Min Wang
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, No. 36, Sanhao Street, Shenyang, Liaoning, 110004, People's Republic of China
| | - Yaodong Dong
- Department of Otolaryngology Head and Neck Surgery, Shengjing Hospital of China Medical University, No. 36, Sanhao Street, Shenyang, Liaoning, 110004, People's Republic of China.
| | - Yingying Zhou
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, No. 36, Sanhao Street, Shenyang, Liaoning, 110004, People's Republic of China.
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7
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Zhao N, Wang J, Huang S, Zhang J, Bao J, Ni H, Gao X, Zhang C. The landscape of programmed cell death-related lncRNAs in Alzheimer's disease and Parkinson's disease. Apoptosis 2024:10.1007/s10495-024-01984-z. [PMID: 38853201 DOI: 10.1007/s10495-024-01984-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/23/2024] [Indexed: 06/11/2024]
Abstract
This study delivers a thorough analysis of long non-coding RNAs (lncRNAs) in regulating programmed cell death (PCD), vital for neurodegenerative diseases like Alzheimer's disease (AD) and Parkinson's disease (PD). We propose a new framework PCDLnc, and identified 20 significant lncRNAs, including HEIH, SNHG15, and SNHG5, associated with PCD gene sets, which were known for roles in proliferation and apoptosis in neurodegenerative diseases. By using GREAT software, we identified regulatory functions of top lncRNAs in different neurodegenerative diseases. Moreover, lncRNAs cis-regulated mRNAs linked to neurodegeneration, including JAK2, AKT1, EGFR, CDC42, SNCA, and ADIPOQ, highlighting their therapeutic potential in neurodegenerative diseases. A further exploration into the differential expression of mRNA identified by PCDLnc revealed a role in apoptosis, ferroptosis and autophagy. Additionally, protein-protein interaction (PPI) network analysis exposed abnormal interactions among key genes, despite their consistent expression levels between disease and normal samples. The randomforest model effectively distinguished between disease samples, indicating a high level of accuracy. Shared gene subsets in AD and PD might serve as potential biomarkers, along with disease-specific gene sets. Besides, we also found the strong relationship between AD and immune infiltration. This research highlights the role of lncRNAs and their associated genes in PCD in neurodegenerative diseases, offering potential therapeutic targets and diagnostic markers for future study and clinical application.
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Affiliation(s)
- Ning Zhao
- College of Computer and Control Engineering, Northeast Forestry University, Harbin, Heilongjiang, China
| | - Junyi Wang
- College of Computer and Control Engineering, Northeast Forestry University, Harbin, Heilongjiang, China
| | - Shan Huang
- The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, China
| | - Jingyu Zhang
- The Fourth Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, China
| | - Jin Bao
- College of Computer and Control Engineering, Northeast Forestry University, Harbin, Heilongjiang, China
| | - Haisen Ni
- College of Computer and Control Engineering, Northeast Forestry University, Harbin, Heilongjiang, China
| | - Xinhang Gao
- College of Computer and Control Engineering, Northeast Forestry University, Harbin, Heilongjiang, China
| | - Chunlong Zhang
- College of Computer and Control Engineering, Northeast Forestry University, Harbin, Heilongjiang, China.
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8
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Saeinasab M, Atlasi Y, M Matin M. Functional role of lncRNAs in gastrointestinal malignancies: the peculiar case of small nucleolar RNA host gene family. FEBS J 2024; 291:1353-1385. [PMID: 36282516 DOI: 10.1111/febs.16668] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2022] [Revised: 09/18/2022] [Accepted: 10/24/2022] [Indexed: 11/06/2022]
Abstract
Long noncoding RNAs (lncRNAs) play crucial roles in normal physiology and are often de-regulated in disease states such as cancer. Recently, a class of lncRNAs referred to as the small nucleolar RNA host gene (SNHG) family have emerged as important players in tumourigenesis. Here, we discuss new findings describing the role of SNHGs in gastrointestinal tumours and summarize the three main functions by which these lncRNAs promote carcinogenesis, namely: competing with endogenous RNAs, modulating protein function, and regulating epigenetic marking. Furthermore, we discuss how SNHGs participate in different hallmarks of cancer, and how this class of lncRNAs may serve as potential biomarkers in cancer diagnosis and therapy.
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Affiliation(s)
- Morvarid Saeinasab
- Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Iran
| | - Yaser Atlasi
- Patrick G. Johnston Centre for Cancer Research, Queen's University Belfast, UK
| | - Maryam M Matin
- Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Iran
- Novel Diagnostics and Therapeutics Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Iran
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9
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Jasim SA, Al-Hawary SIS, Hjazi A, Ahmad I, Kaur I, Kadhum WR, Alkhafaji AT, Ghildiyal P, Jawad MA, Alsaadi SB. A comprehensive review of lncRNA CRNDE in cancer progression and pathology, with a specific glance at the epithelial-mesenchymal transition (EMT) process. Pathol Res Pract 2024; 256:155229. [PMID: 38484655 DOI: 10.1016/j.prp.2024.155229] [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: 01/21/2024] [Revised: 02/09/2024] [Accepted: 02/25/2024] [Indexed: 04/14/2024]
Abstract
It has been suggested that the long non-coding RNAs (lncRNAs), such as colorectal neoplasia differentially expressed (CRNDE), may contribute to the formation of human cancer. It is yet unknown, though, what therapeutic significance CRNDE expression has for different forms of cancer. CRNDE has recently been proposed as a possible diagnostic biomarker and prognostic pred for excellent specificity and sensitivity in cancer tissues and plasma. To provide the groundwork for potential future therapeutic uses of CRNDE, we briefly overview its biological action and related cancer-related pathways. Next, we mainly address the impact of CRNDE on the epithelial-mesenchymal transition (EMT). The epithelial-mesenchymal transition, or EMT, is an essential biological mechanism involved in the spread of cancer.
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Affiliation(s)
| | | | - Ahmed Hjazi
- Department of Medical Laboratory, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
| | - Irfan Ahmad
- Department of Clinical Laboratory Sciences, College of Applied Medical Science, King Khalid University, Abha, Saudi Arabia.
| | - Irwanjot Kaur
- Department of Biotechnology and Genetics, Jain (Deemed-to-be) University, Bengaluru, Karnataka 560069, India; Department of Allied Healthcare and Sciences, Vivekananda Global University, Jaipur, Rajasthan 303012, India
| | - Wesam R Kadhum
- Department of Pharmacy, Kut University College, Kut, Wasit 52001, Iraq; Advanced research center, Kut University College, Kut, Wasit 52001, Iraq
| | | | - Pallavi Ghildiyal
- Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun, India
| | | | - Salim B Alsaadi
- Department of Pharmaceutics, Al-Hadi University College, Baghdad 10011, Iraq
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10
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Oh CK, Cho YS. Pathogenesis and biomarkers of colorectal cancer by epigenetic alteration. Intest Res 2024; 22:131-151. [PMID: 38295766 PMCID: PMC11079515 DOI: 10.5217/ir.2023.00115] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2023] [Revised: 11/16/2023] [Accepted: 12/29/2023] [Indexed: 05/12/2024] Open
Abstract
Colorectal cancer (CRC) ranks third in cancer incidence and stands as the second leading cause of cancer-related deaths globally. CRC tumorigenesis results from a cumulative set of genetic and epigenetic alterations, disrupting cancer-regulatory processes like cell proliferation, metabolism, angiogenesis, cell death, invasion, and metastasis. Key epigenetic modifications observed in cancers encompass abnormal DNA methylation, atypical histone modifications, and irregularities in noncoding RNAs, such as microRNAs and long noncoding RNAs. The advancement in genomic technologies has positioned these genetic and epigenetic shifts as potential clinical biomarkers for CRC patients. This review concisely covers the fundamental principles of CRC-associated epigenetic changes, and examines in detail their emerging role as biomarkers for early detection, prognosis, and treatment response prediction.
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Affiliation(s)
- Chang Kyo Oh
- Division of Gastroenterology, Department of Internal Medicine, Hallym University Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea
| | - Young-Seok Cho
- Division of Gastroenterology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
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11
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Wu ZH, Wang YX, Song JJ, Zhao LQ, Zhai YJ, Liu YF, Guo WJ. LncRNA SNHG26 promotes gastric cancer progression and metastasis by inducing c-Myc protein translation and an energy metabolism positive feedback loop. Cell Death Dis 2024; 15:236. [PMID: 38553452 PMCID: PMC10980773 DOI: 10.1038/s41419-024-06607-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2023] [Revised: 03/07/2024] [Accepted: 03/11/2024] [Indexed: 04/02/2024]
Abstract
Metastasis is a bottleneck in cancer treatment. Studies have shown the pivotal roles of long noncoding RNAs (lncRNAs) in regulating cancer metastasis; however, our understanding of lncRNAs in gastric cancer (GC) remains limited. RNA-seq was performed on metastasis-inclined GC tissues to uncover metastasis-associated lncRNAs, revealing upregulated small nucleolar RNA host gene 26 (SNHG26) expression, which predicted poor GC patient prognosis. Functional experiments revealed that SNHG26 promoted cellular epithelial-mesenchymal transition and proliferation in vitro and in vivo. Mechanistically, SNHG26 was found to interact with nucleolin (NCL), thereby modulating c-Myc expression by increasing its translation, and in turn promoting energy metabolism via hexokinase 2 (HK2), which facilitates GC malignancy. The increase in energy metabolism supplies sufficient energy to promote c-Myc translation and expression, forming a positive feedback loop. In addition, metabolic and translation inhibitors can block this loop, thus inhibiting cell proliferation and mobility, indicating potential therapeutic prospects in GC.
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Affiliation(s)
- Zhen-Hua Wu
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Yi-Xuan Wang
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Jun-Jiao Song
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Shanghai, 200032, China
| | - Li-Qin Zhao
- Department of Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Yu-Jia Zhai
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Yan-Fang Liu
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Shanghai, 200032, China
| | - Wei-Jian Guo
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
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12
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Yang Z, Pan J, Zhou C, Yu C, Zhou Z, Ding G, Liu X, Sheng J, Jin L, Huang H. LncRNA SNHG5 adversely governs follicular growth in PCOS via miR-92a-3p/CDKN1C axis. iScience 2024; 27:108522. [PMID: 38313057 PMCID: PMC10835362 DOI: 10.1016/j.isci.2023.108522] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2023] [Revised: 11/13/2023] [Accepted: 11/20/2023] [Indexed: 02/06/2024] Open
Abstract
Small nucleolar RNA host genes (SNHGs) have been implicated in various biological processes, yet their involvement in polycystic ovary syndrome (PCOS) remains elusive. Specifically, SNHG5, a long non-coding RNA implicated in several human cancers, shows elevated expression in granulosa cells (GCs) of PCOS women and induces PCOS-like features when overexpressed in mice. In vitro, SNHG5 inhibits GC proliferation and induces apoptosis and cell-cycle arrest at G0/G1 phase, with RNA-seq indicating its impact on DNA replication and repair pathways. Mechanistically, SNHG5 acts as a competing endogenous RNA by binding to miR-92a-3p, leading to increased expression of target gene CDKN1C, which further suppresses GC proliferation and promotes apoptosis. These findings elucidate the crucial role of SNHG5 in the pathogenesis of PCOS and suggest a potential therapeutic target for this condition. Additional investigations such as large-scale clinical studies and functional assays are warranted to validate and expand upon these findings.
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Affiliation(s)
- Zuwei Yang
- Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai, China
- The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- Research Units of Embryo Original Diseases, Chinese Academy of Medical Sciences (No. 2019RU056), Shanghai, China
| | - Jiexue Pan
- Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai, China
- Research Units of Embryo Original Diseases, Chinese Academy of Medical Sciences (No. 2019RU056), Shanghai, China
| | - Chengliang Zhou
- The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Chuanjin Yu
- Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai, China
| | - Zhiyang Zhou
- Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai, China
| | - Guolian Ding
- Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai, China
| | - Xinmei Liu
- Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai, China
| | - Jianzhong Sheng
- Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai, China
| | - Li Jin
- Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai, China
- Research Units of Embryo Original Diseases, Chinese Academy of Medical Sciences (No. 2019RU056), Shanghai, China
| | - Hefeng Huang
- Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai, China
- The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- Research Units of Embryo Original Diseases, Chinese Academy of Medical Sciences (No. 2019RU056), Shanghai, China
- Shanghai Key Laboratory of Reproduction and Development, Shanghai, China
- Key Laboratory of Reproductive Genetics (Ministry of Education), Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China
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13
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Pashirzad M, Sahebkar A. The Prognostic Value and Clinical Significance of lncRNA SNHG5 Expression in Patients with Multiple Malignancies: A Bioinformatic and Meta-analysis. Curr Cancer Drug Targets 2024; 24:1286-1297. [PMID: 38409690 DOI: 10.2174/0115680096282865240111055640] [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: 10/26/2023] [Revised: 12/28/2023] [Accepted: 01/03/2024] [Indexed: 02/28/2024]
Abstract
BACKGROUND Long non-coding RNA small nucleolar RNA host gene 5 (lncRNA SNHG5) has been identified as both a promising target for treatment and a predictor of prognosis in diverse types of cancer. The objective of this study was to assess whether lncRNA SNHG5 expression can be utilized as a prognostic biomarker for human cancer. METHODS To ensure a thorough search of the literature for relevant English studies published before July 2023, several databases were searched, including PubMed, Web of Science, ProQuest, Cochrane Library, and Google Scholar. The study evaluated the impact of lncRNA SNHG5 on the overall survival (OS) of cancer by calculating the pooled hazard ratio (HR) and odds ratio (OR) with 95% confidence intervals (CIs). To further confirm the accuracy of the findings, the study investigated the expression profile and prognostic significance of lncRNA SNHG5 through the use of GenomicScape, OncoLnc, Kaplan-Meier plotter, and GEPIA databases. RESULTS In this study, 995 patients were examined across a total of fourteen original studies. The findings indicated that there was a significant relationship between heightened lncRNA SNHG5 expression and reduced OS, as evidenced by both univariate and multivariate analyses (HR = 1.89; 95% CI, 1.44-2.49; p < 0.001; HR = 3.97; 95% CI, 1.80-8.73; p < 0.001, respectively). Pooled OR analysis showed a significant association between over-expression of lncRNA SNHG5 with advanced histological grade (OR = 0.28; 95% CI, 0.11-0.71; p = 0.007), present lymph node metastasis (LNM; OR = 4.28; 95% CI, 2.47-7.43; p < 0.001), and smoking history (OR = 0.27; 95% CI, 0.15-0.49; p < 0.001). Bioinformatic databases confirmed that elevated SNHG5 expression was significantly linked to poor prognosis in cancer patients, including colorectal cancer (CRC), acute myeloid leukemia (AML), and esophageal adenocarcinoma (ESAD), and a longer OS in patients with uterine corpus endometrial carcinoma (UCEC). CONCLUSION These results suggest that lncRNA SNHG5 may serve as an adverse prognostic biomarker in several human cancers. Further investigations are needed to better understand the underlying mechanisms that link lncRNA SNHG5 to multiple malignancies.
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Affiliation(s)
- Mehran Pashirzad
- Department of Medical Biochemistry, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amirhossein Sahebkar
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
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14
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Monziani A, Ulitsky I. Noncoding snoRNA host genes are a distinct subclass of long noncoding RNAs. Trends Genet 2023; 39:908-923. [PMID: 37783604 DOI: 10.1016/j.tig.2023.09.001] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Revised: 09/04/2023] [Accepted: 09/07/2023] [Indexed: 10/04/2023]
Abstract
Mammalian genomes are pervasively transcribed into different noncoding (nc)RNA classes, each one with its own hallmarks and exceptions. Some of them are nested into each other, such as host genes for small nucleolar RNAs (snoRNAs), which were long believed to simply act as molecular containers strictly facilitating snoRNA biogenesis. However, recent findings show that noncoding snoRNA host genes (ncSNHGs) display features different from those of 'regular' long ncRNAs (lncRNAs) and, more importantly, they can exert independent and unrelated functions to those of the encoded snoRNAs. Here, we review and summarize past and recent evidence that ncSNHGs form a defined subclass among the plethora of lncRNAs, and discuss future research that can further elucidate their biological relevance.
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Affiliation(s)
- Alan Monziani
- Department of Immunology and Regenerative Biology, Weizmann Institute of Science, 7610001 Rehovot, Israel; Department of Molecular Neuroscience, Weizmann Institute of Science, 7610001 Rehovot, Israel
| | - Igor Ulitsky
- Department of Immunology and Regenerative Biology, Weizmann Institute of Science, 7610001 Rehovot, Israel; Department of Molecular Neuroscience, Weizmann Institute of Science, 7610001 Rehovot, Israel.
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15
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Almasi S, SarmastiEmami S, Baird S, Ning Z, Figeys D, Côté J, Cowan KN, Jasmin BJ. Staufen1 controls mitochondrial metabolism via HIF2α in embryonal rhabdomyosarcoma and promotes tumorigenesis. Cell Mol Life Sci 2023; 80:328. [PMID: 37847286 PMCID: PMC11071833 DOI: 10.1007/s00018-023-04969-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2023] [Revised: 08/31/2023] [Accepted: 09/18/2023] [Indexed: 10/18/2023]
Abstract
Elevated mitochondrial metabolism promotes tumorigenesis of Embryonal Rhabdomyosarcomas (ERMS). Accordingly, targeting oxidative phosphorylation (OXPHOS) could represent a therapeutic strategy for ERMS. We previously demonstrated that genetic reduction of Staufen1 (STAU1) levels results in the inhibition of ERMS tumorigenicity. Here, we examined STAU1-mediated mechanisms in ERMS and focused on its potential involvement in regulating OXPHOS. We report the novel and differential role of STAU1 in mitochondrial metabolism in cancerous versus non-malignant skeletal muscle cells (NMSkMCs). Specifically, our data show that STAU1 depletion reduces OXPHOS and inhibits proliferation of ERMS cells. Our findings further reveal the binding of STAU1 to several OXPHOS mRNAs which affects their stability. Indeed, STAU1 depletion reduced the stability of OXPHOS mRNAs, causing inhibition of mitochondrial metabolism. In parallel, STAU1 depletion impacted negatively the HIF2α pathway which further modulates mitochondrial metabolism. Exogenous expression of HIF2α in STAU1-depleted cells reversed the mitochondrial inhibition and induced cell proliferation. However, opposite effects were observed in NMSkMCs. Altogether, these findings revealed the impact of STAU1 in the regulation of mitochondrial OXPHOS in cancer cells as well as its differential role in NMSkMCs. Overall, our results highlight the therapeutic potential of targeting STAU1 as a novel approach for inhibiting mitochondrial metabolism in ERMS.
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Affiliation(s)
- Shekoufeh Almasi
- Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, K1H 8M5, Canada
| | - Sahar SarmastiEmami
- Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, K1H 8M5, Canada
| | - Stephen Baird
- High Throughput Lab, CHEO, University of Ottawa, Ottawa, ON, K1H 8L1, Canada
| | - Zhibin Ning
- School of Pharmaceutical Sciences, Faculty of Medicine, University of Ottawa, Ottawa, ON, K1H 8M5, Canada
| | - Daniel Figeys
- School of Pharmaceutical Sciences, Faculty of Medicine, University of Ottawa, Ottawa, ON, K1H 8M5, Canada
| | - Jocelyn Côté
- Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, K1H 8M5, Canada
- The Eric J. Poulin Centre for Neuromuscular Diseases, Faculty of Medicine, University of Ottawa, Ottawa, ON, K1H 8M5, Canada
| | - Kyle N Cowan
- Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, K1H 8M5, Canada
- Department of Surgery, Division of Paediatric Surgery, University of Ottawa, Children's Hospital of Eastern Ontario, Ottawa, ON, K1Y 4E9, Canada
- Molecular Biomedicine Program, Children's Hospital of Eastern Ontario, Ottawa, ON, K1H 8L1, Canada
| | - Bernard J Jasmin
- Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, K1H 8M5, Canada.
- The Eric J. Poulin Centre for Neuromuscular Diseases, Faculty of Medicine, University of Ottawa, Ottawa, ON, K1H 8M5, Canada.
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16
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Huldani H, Gandla K, Asiri M, Romero-Parra RM, Alsalamy A, Hjazi A, Najm MAA, Fawaz A, Hussien BM, Singh R. A comprehensive insight into the role of small nucleolar RNAs (snoRNAs) and SNHGs in human cancers. Pathol Res Pract 2023; 249:154679. [PMID: 37567032 DOI: 10.1016/j.prp.2023.154679] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2023] [Revised: 07/04/2023] [Accepted: 07/07/2023] [Indexed: 08/13/2023]
Abstract
Long non-coding RNAs (lncRNAs), which comprise most non-coding RNAs (ncRNAs), have recently become a focus of cancer research. How many functional ncRNAs exist is still a matter of debate. Although insufficient evidence supports that most lncRNAs function as transcriptional by-products, it is widely known that an increasing number of lncRNAs play essential roles in cells. Small nucleolar RNAs (snoRNAs), 60-300 nucleotides in length, have been better studied than long non-coding RNAs (lncRNAs) and are predominantly present in the nucleolus. Most snoRNAs are encoded in introns of protein- and non-protein-coding genes called small nucleolar RNA host genes (SNHGs). In this article, we explore the biology and characteristics of SNHGs and their role in developing human malignancies. In addition, we provide an update on the ability of these snoRNAs to serve as prognostic and diagnostic variables in various forms of cancer.
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Affiliation(s)
- Huldani Huldani
- Department of Physiology, Faculty of Medicine, Lambung Mangkurat University, Banjarmasin, South Kalimantan, Indonesia
| | - Kumaraswamy Gandla
- Department of Pharmaceutical Analysis, Chaitanya Deemed to be University, Hanamkonda, India.
| | - Mohammed Asiri
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia
| | | | - Ali Alsalamy
- College of Medical Technology, Imam Ja'afar Al-Sadiq University, Al-Muthanna 66002, Iraq
| | - Ahmed Hjazi
- Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
| | - Mazin A A Najm
- Pharmaceutical Chemistry Department, College of Pharmacy, Al-Ayen University, Thi-Qar, Iraq
| | - Albab Fawaz
- Medical Technical College, Al-Farahidi University, Baghdad, Iraq
| | - Beneen M Hussien
- Medical Laboratory Technology Department, College of Medical Technology, The Islamic University, Najaf, Iraq
| | - Rajesh Singh
- Uttaranchal Institute of Technology, Uttaranchal University, Dehradun 248007, India
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17
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Xiao H, Feng X, Liu M, Gong H, Zhou X. SnoRNA and lncSNHG: Advances of nucleolar small RNA host gene transcripts in anti-tumor immunity. Front Immunol 2023; 14:1143980. [PMID: 37006268 PMCID: PMC10050728 DOI: 10.3389/fimmu.2023.1143980] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Accepted: 03/03/2023] [Indexed: 03/17/2023] Open
Abstract
The small nucleolar RNA host genes (SNHGs) are a group of genes that can be transcript into long non-coding RNA SNHG (lncSNHG) and further processed into small nucleolar RNAs (snoRNAs). Although lncSNHGs and snoRNAs are well established to play pivotal roles in tumorigenesis, how lncSNHGs and snoRNAs regulate the immune cell behavior and function to mediate anti-tumor immunity remains further illustrated. Certain immune cell types carry out distinct roles to participate in each step of tumorigenesis. It is particularly important to understand how lncSNHGs and snoRNAs regulate the immune cell function to manipulate anti-tumor immunity. Here, we discuss the expression, mechanism of action, and potential clinical relevance of lncSNHGs and snoRNAs in regulating different types of immune cells that are closely related to anti-tumor immunity. By uncovering the changes and roles of lncSNHGs and snoRNAs in different immune cells, we aim to provide a better understanding of how the transcripts of SNHGs participate in tumorigenesis from an immune perspective.
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Affiliation(s)
- Hao Xiao
- Department of Clinical Laboratory Medicine, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
- Department of Clinical Laboratory Medicine, Xiangya School of Medicine, Central South University, Changsha, Hunan, China
| | - Xin Feng
- Department of Clinical Laboratory Medicine, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
- Department of Clinical Laboratory Medicine, Xiangya School of Medicine, Central South University, Changsha, Hunan, China
| | - Mengjun Liu
- Department of Clinical Laboratory Medicine, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
- Department of Clinical Laboratory Medicine, Xiangya School of Medicine, Central South University, Changsha, Hunan, China
| | - Hanwen Gong
- Department of Clinical Laboratory Medicine, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
- Department of Clinical Laboratory Medicine, Xiangya School of Medicine, Central South University, Changsha, Hunan, China
| | - Xiao Zhou
- Department of Clinical Laboratory Medicine, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
- Department of Clinical Laboratory Medicine, Xiangya School of Medicine, Central South University, Changsha, Hunan, China
- *Correspondence: Xiao Zhou,
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18
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Wu Y, Xu X. Long non-coding RNA signature in colorectal cancer: research progression and clinical application. Cancer Cell Int 2023; 23:28. [PMID: 36797749 PMCID: PMC9936661 DOI: 10.1186/s12935-023-02867-0] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2022] [Accepted: 02/05/2023] [Indexed: 02/18/2023] Open
Abstract
Colorectal cancer is one of the top-ranked human malignancies. The development and progression of colorectal cancer are associated with aberrant expression of multiple coding and non-coding genes. Long non-coding RNAs (lncRNAs) have an important role in regulating gene stability as well as gene expression. Numerous current studies have shown that lncRNAs are promising biomarkers and therapeutic targets for colorectal cancer. In this review, we have searched the available literature to list lncRNAs involved in the pathogenesis and regulation of colorectal cancer. We focus on the role of lncRNAs in cancer promotion or suppression, their value in tumor diagnosis, and their role in treatment response and prognosis prediction. In addition, we will discuss the signaling pathways that these lncRNAs are mainly associated with in colorectal cancer. We also summarize the role of lncRNAs in colorectal precancerous lesions and colorectal cancer consensus molecular subgroups. We hope this review article will bring you the latest research progress and outlook on lncRNAs in colorectal cancer.
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Affiliation(s)
- Yudi Wu
- grid.33199.310000 0004 0368 7223GI Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, People’s Republic of China ,grid.33199.310000 0004 0368 7223Department of Gastrointestinal Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030 People’s Republic of China
| | - Xiangshang Xu
- GI Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, People's Republic of China. .,Department of Gastrointestinal Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, People's Republic of China.
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19
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LncRNA SNHG5 Suppresses Cell Migration and Invasion of Human Lung Adenocarcinoma via Regulation of Epithelial-Mesenchymal Transition. JOURNAL OF ONCOLOGY 2023; 2023:3335959. [PMID: 36711024 PMCID: PMC9879674 DOI: 10.1155/2023/3335959] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Revised: 11/01/2022] [Accepted: 11/09/2022] [Indexed: 01/21/2023]
Abstract
Long noncoding RNAs (lncRNAs) are gradually being annotated as important regulators of multiple cellular processes. The goal of our study was to investigate the effects of the lncRNA small nucleolar RNA host gene 5 (SNHG5) in lung adenocarcinoma (LAD) and its underlying mechanisms. The findings revealed a substantial drop in SNHG5 expression in LAD tissues, which correlated with clinical-pathological parameters. Transcriptome sequencing analysis demonstrated that the inhibitory effect of SNHG5 was associated with cell adhesion molecules. Moreover, the expression of SNHG5 was shown to be correlated with epithelial-mesenchymal transition (EMT) markers in western blots and immunofluorescence. SNHG5 also had significant effects of antimigration and anti-invasion on LAD cells in vitro. Furthermore, the migration and invasion of A549 cells were suppressed by overexpressed SNHG5 in the EMT progress induced by transforming growth factor β1 (TGF-β1), and this might be due to the inhibition of the expression of EMT-associated transcription factors involving Snail, SLUG, and ZEB1. In LAD tissues, the expression of SNHG5 exhibited a positive association with E-cadherin protein expression but a negative correlation with N-cadherin and vimentin, according to the results of quantitative real-time PCR (qRT-PCR). In summary, the current work demonstrated that the lncRNA SNHG5 might limit cell migration and invasion of LAD cancer via decreasing the EMT process, indicating that SNHG5 might be used as a target for LAD therapeutic methods.
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20
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Transcriptomic Analysis of Long Non-Coding RNA during Candida albicans Infection. Genes (Basel) 2023; 14:genes14020251. [PMID: 36833177 PMCID: PMC9956080 DOI: 10.3390/genes14020251] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Revised: 01/07/2023] [Accepted: 01/16/2023] [Indexed: 01/20/2023] Open
Abstract
Candida albicans is one of the most commonly found species in fungal infections. Due to its clinical importance, molecular aspects of the host immune defense against the fungus are of interest to biomedical sciences. Long non-coding RNAs (lncRNAs) have been investigated in different pathologies and gained widespread attention regarding their role as gene regulators. However, the biological processes in which most lncRNAs perform their function are still unclear. This study investigates the association between lncRNAs with host response to C. albicans using a public RNA-Seq dataset from lung samples of female C57BL/6J wild-type Mus musculus with induced C. albicans infection. The animals were exposed to the fungus for 24 h before sample collection. We selected lncRNAs and protein-coding genes related to the host immune response by combining the results from different computational approaches used for gene selection: differential expression gene analysis, co-expression genes network analysis, and machine learning-based gene selection. Using a guilt by association strategy, we inferred connections between 41 lncRNAs and 25 biological processes. Our results indicated that nine up-regulated lncRNAs were associated with biological processes derived from the response to wounding: 1200007C13Rik, 4833418N02Rik, Gm12840, Gm15832, Gm20186, Gm38037, Gm45774, Gm4610, Mir22hg, and Mirt1. Additionally, 29 lncRNAs were related to genes involved in immune response, while 22 lncRNAs were associated with processes related to reactive species production. These results support the participation of lncRNAs during C. albicans infection, and may contribute to new studies investigating lncRNA functions in the immune response.
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21
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Lin J, Yan J, Deng XL, Wang CS, Wang HS. SPATS2 is correlated with cell cycle progression and immune cells infiltration in hepatocellular carcinoma. BMC Gastroenterol 2023; 23:8. [PMID: 36631750 PMCID: PMC9832668 DOI: 10.1186/s12876-022-02633-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Accepted: 12/22/2022] [Indexed: 01/12/2023] Open
Abstract
The spermatogenesis associated serine rich 2 (SPATS2) is a member of RNA-binding protein in which the abnormal expression is linked with carcinogenesis in serval types of cancer. However, there is no systematic study on the differential expression, prognostic significance, epigenetic regulation, immune infiltration of SPATS2 in hepatocellular carcinoma (HCC). In the present study, we investigated the expression, prognosis, epigenetic regulation, and immune cell infiltration of SPATS2 in HCC. We found that the elevated expression of SPATS2 was unfavorably associated with the clinical pathological stage and prognosis. Functional enrichment analysis revealed that SPATS2 is associated with cell cycle, apoptosis and cancer cell metastasis processes in HCC. Our results confirmed that knockdown of SPATS2 will affect cell cycle, apoptosis and invasion of HCC cell lines. Moreover, the expression of SPATS2 is upregulated by epigenetic regulation, including DNA methylation, m6A and histone modification in HCC. In addition, SPATS2 expression was positively correlated with immune cell infiltration or expression of immune related gene markers in HCC. Taken together, our data demonstrated that SPATS2 is associated with progression and immune infiltration, and could serve as a prognostic biomarker for HCC. In conclusion, these results highlight the potential of SPATS2 to be used as a therapeutic target for HCC.
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Affiliation(s)
- Jing Lin
- grid.411643.50000 0004 1761 0411College of Life Science, Inner Mongolia University, Hohhot, Inner Mongolia China
| | - Jia Yan
- grid.410612.00000 0004 0604 6392School of Basic Medical, Inner Mongolia Medical University, Hohhot, Inner Mongolia China
| | - Xiu ling Deng
- grid.410612.00000 0004 0604 6392School of Basic Medical, Inner Mongolia Medical University, Hohhot, Inner Mongolia China
| | - Chang shan Wang
- grid.411643.50000 0004 1761 0411College of Life Science, Inner Mongolia University, Hohhot, Inner Mongolia China
| | - Hai sheng Wang
- grid.410612.00000 0004 0604 6392School of Basic Medical, Inner Mongolia Medical University, Hohhot, Inner Mongolia China
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22
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Luo ZD, Wang YF, Zhao YX, Yu LC, Li T, Fan YJ, Zeng SJ, Zhang YL, Zhang Y, Zhang X. Emerging roles of non-coding RNAs in colorectal cancer oxaliplatin resistance and liquid biopsy potential. World J Gastroenterol 2023; 29:1-18. [PMID: 36683709 PMCID: PMC9850945 DOI: 10.3748/wjg.v29.i1.1] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2022] [Revised: 10/11/2022] [Accepted: 11/04/2022] [Indexed: 01/04/2023] Open
Abstract
Colorectal cancer (CRC) is one of the most common malignancies of the digestive tract, with the annual incidence and mortality increasing consistently. Oxaliplatin-based chemotherapy is a preferred therapeutic regimen for patients with advanced CRC. However, most patients will inevitably develop resistance to oxaliplatin. Many studies have reported that non-coding RNAs (ncRNAs), such as microRNAs, long non-coding RNAs, and circular RNAs, are extensively involved in cancer progression. Moreover, emerging evidence has revealed that ncRNAs mediate chemoresistance to oxaliplatin by transcriptional and post-transcriptional regulation, and by epigenetic modification. In this review, we summarize the mechanisms by which ncRNAs regulate the initiation and development of CRC chemoresistance to oxaliplatin. Furthermore, we investigate the clinical application of ncRNAs as promising biomarkers for liquid CRC biopsy. This review provides new insights into overcoming oxaliplatin resistance in CRC by targeting ncRNAs.
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Affiliation(s)
- Zheng-Dong Luo
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, Jinan 250012, Shandong Province, China
| | - Yi-Feng Wang
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, Jinan 250012, Shandong Province, China
| | - Yu-Xiao Zhao
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, Jinan 250012, Shandong Province, China
| | - Long-Chen Yu
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, Jinan 250012, Shandong Province, China
| | - Tian Li
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, Jinan 250012, Shandong Province, China
| | - Ying-Jing Fan
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, Jinan 250012, Shandong Province, China
| | - Shun-Jie Zeng
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, Jinan 250012, Shandong Province, China
| | - Yan-Li Zhang
- Department of Clinical Laboratory, Shandong Provincial Third Hospital, Jinan 250012, Shandong Province, China
| | - Yi Zhang
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, Jinan 250012, Shandong Province, China
| | - Xin Zhang
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, Jinan 250012, Shandong Province, China
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23
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Endogenous retroelements as alarms for disruptions to cellular homeostasis. Trends Cancer 2023; 9:55-68. [PMID: 36216729 DOI: 10.1016/j.trecan.2022.09.001] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2022] [Revised: 08/28/2022] [Accepted: 09/07/2022] [Indexed: 11/05/2022]
Abstract
Endogenous retroelements are DNA sequences which can duplicate and move to new locations in the genome. Actively moving endogenous retroelements can be disruptive to the host, and their expression is therefore often repressed. Interestingly, drugs that disrupt the repression of endogenous retroelements show promise for treating cancer. Expressed endogenous retroelements can activate innate immune receptors that activate the antiviral response, potentially leading to the death of cancer cells. We discuss disruptions to cellular processes which can lead to activation of the antiviral state from endogenous retroelements, and present the 'fire alarm hypothesis', where we argue that endogenous retroelements act as alarms for disruptions to these cellular processes. Furthermore, we discuss the properties of endogenous retroelements which make them suitable as alarms.
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24
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Shetty A, Venkatesh T, Kabbekodu SP, Tsutsumi R, Suresh PS. LncRNA-miRNA-mRNA regulatory axes in endometrial cancer: a comprehensive overview. Arch Gynecol Obstet 2022; 306:1431-1447. [PMID: 35182183 DOI: 10.1007/s00404-022-06423-5] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Accepted: 01/24/2022] [Indexed: 12/12/2022]
Abstract
INTRODUCTION Recent research on tumorigenesis and progression has opened up an array of novel molecular mechanisms in the form of interactions between cellular non-coding RNAs (long non-coding RNA[lncRNA]/microRNA [miRNA]) and coding transcripts that regulate health and disease. Endometrial cancer (EC) is a prominent gynecological malignancy with a high incidence rate and poorly known etiology and prognostic factors that hinder the success of disease management. The emerging role of lncRNA-miRNA-mRNA interactions and their dysregulation in the pathophysiology of EC has been elucidated in many recent studies. METHODS A thorough literature review was conducted to explore information about lncRNA-miRNA-mRNA axes in EC. RESULTS Several lncRNAs act as molecular sponges that sequester various tumor suppressor miRNAs to inhibit their function, leading to the dysregulation of their target mRNA transcripts that contribute to the EC regulation. CONCLUSIONS This review summarizes these networks of molecular mechanisms and their contribution to different aspects of endometrial carcinogenesis, leading to a better conceptualization of the molecular pathways that underlie the disease and helping establish novel diagnostic biomarkers and therapeutic intervention points to aid the curative intent of EC.
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Affiliation(s)
- Abhishek Shetty
- Department of Biosciences, Mangalore University, Mangalagangothri, Mangalore, 574 199, Karnataka, India
| | - Thejaswini Venkatesh
- Department of Biochemistry and Molecular Biology, Central University of Kerala, Kasargod, 671316, Kerala, India
| | - Shama Prasada Kabbekodu
- Department of Cell and Molecular Biology, School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Rie Tsutsumi
- Department of Nutrition and Metabolism, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto-cho, Tokushima City, 770-8503, Japan
| | - Padmanaban S Suresh
- School of Biotechnology, National Institute of Technology, Calicut, 673601, Kerala, India.
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25
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Zhou Y, Li ZL, Ding L, Zhang XJ, Liu NC, Liu SS, Wang YF, Ma RX. Long noncoding RNA SNHG5 promotes podocyte injury via the microRNA-26a-5p/TRPC6 pathway in diabetic nephropathy. J Biol Chem 2022; 298:102605. [PMID: 36257404 PMCID: PMC9694110 DOI: 10.1016/j.jbc.2022.102605] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Revised: 10/09/2022] [Accepted: 10/10/2022] [Indexed: 11/05/2022] Open
Abstract
Podocyte injury is a characteristic pathological hallmark of diabetic nephropathy (DN). However, the exact mechanism of podocyte injury in DN is incompletely understood. This study was conducted using db/db mice and immortalized mouse podocytes. High-throughput sequencing was used to identify the differentially expressed long noncoding RNAs in kidney of db/db mice. The lentiviral shRNA directed against long noncoding RNA small nucleolar RNA host gene 5 (SNHG5) or microRNA-26a-5p (miR-26a-5p) agomir was used to treat db/db mice to regulate the SNHG5/miR-26a-5p pathway. Here, we found that the expression of transient receptor potential canonical type 6 (TRPC6) was significantly increased in injured podocytes under the condition of DN, which was associated with markedly decreased miR-26a-5p. We determined that miR-26a-5p overexpression ameliorated podocyte injury in DN via binding to 3'-UTR of Trpc6, as evidenced by the markedly reduced activity of luciferase reporters by miR-26a-5p mimic. Then, the upregulated SNHG5 in podocytes and kidney in DN was identified, and it was proved to sponge to miR-26a-5p directly using luciferase activity, RNA immunoprecipitation, and RNA pull-down assay. Knockdown of SNHG5 attenuated podocyte injury in vitro, accompanied by an increased expression of miR-26a-5p and decreased expression of TRPC6, demonstrating that SNHG5 promoted podocyte injury by controlling the miR-26a-5p/TRPC6 pathway. Moreover, knockdown of SNHG5 protects against podocyte injury and progression of DN in vivo. In conclusion, SNHG5 promotes podocyte injury via the miR-26a-5p/TRPC6 pathway in DN. Our findings provide novel insights into the pathophysiology of podocyte injury and a potential new therapeutic strategy for DN.
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Affiliation(s)
- Yan Zhou
- Department of Nephrology, Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Zuo-Lin Li
- Institute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing, Jiangsu, China
| | - Lin Ding
- Department of Nephrology, Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Xing-Jian Zhang
- Department of Nephrology, Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Nan-Chi Liu
- Department of Nephrology, Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Shan-Shan Liu
- Department of Nephrology, Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Yan-Fei Wang
- Department of Nephrology, Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Rui-Xia Ma
- Department of Nephrology, Affiliated Hospital of Qingdao University, Qingdao, Shandong, China,For correspondence: Rui-Xia Ma
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26
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Ren L, Fang X, Shrestha SM, Ji Q, Ye H, Liang Y, Liu Y, Feng Y, Dong J, Shi R. LncRNA SNHG16 promotes development of oesophageal squamous cell carcinoma by interacting with EIF4A3 and modulating RhoU mRNA stability. Cell Mol Biol Lett 2022; 27:89. [PMID: 36221055 PMCID: PMC9552503 DOI: 10.1186/s11658-022-00386-w] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Accepted: 09/09/2022] [Indexed: 01/27/2023] Open
Abstract
BACKGROUND Numerous studies have revealed that long noncoding RNAs (lncRNAs) are closely related to the development of many diseases and carcinogenesis. However, their specific biological function and molecular mechanism in oesophageal squamous cell carcinoma (ESCC) remains unclear. METHODS RNA-Seq was performed to determine the differential expressions of lncRNAs in ESCC, and the level of SNHG16 expression was detected in ESCC and intraepithelial neoplasia (IEN) samples. In vitro and in vivo experiments were performed to explore the role of SNHG16 and the interaction of EIF4A3 and Ras homologue family member U (RhoU) signalling. RESULTS One hundred and seventy-five upregulated and 134 downregulated lncRNAs were identified by RNA-Seq. SNHG16 was highly expressed in ESCC and intraepithelial neoplasia (IEN) samples, and its expression level was correlated with tumour differentiation and T stage. Overexpression of SNHG16 can facilitate ESCC cell proliferation and metastasis. Mechanistically, we noticed that SNHG16 could bind RNA binding protein (RBP)-eukaryotic translation initiation factor (EIF4A3) and interact with it to form a complex. Importantly, the coalition of SNHG16 and EIF4A3 ultimately regulated Ras homologue family member U (RhoU). SNHG16 modulated RhoU expression by recruiting EIF4A3 to regulate the stability of RhoU mRNA. Knockdown of RhoU further alleviated the effect of the SNHG16 oncogene in ESCC cells. CONCLUSIONS The newly identified SNHG16-EIF4A3-RhoU signalling pathway directly coordinates the response in ESCC pathogenesis and suggests that SNHG16 is a promising target for potential ESCC treatment.
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Affiliation(s)
- Lihua Ren
- Department of Gastroenterology, Zhongda Hospital, School of Medicine, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, Jiangsu Province, People's Republic of China
| | - Xin Fang
- Department of Gastroenterology, Zhongda Hospital, School of Medicine, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, Jiangsu Province, People's Republic of China
| | - Sachin Mulmi Shrestha
- Department of Gastroenterology, Zhongda Hospital, School of Medicine, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, Jiangsu Province, People's Republic of China
| | - Qinghua Ji
- Department of Gastroenterology, Zhongda Hospital, School of Medicine, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, Jiangsu Province, People's Republic of China
| | - Hui Ye
- Department of Gastroenterology, Zhongda Hospital, School of Medicine, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, Jiangsu Province, People's Republic of China
| | - Yan Liang
- Department of Gastroenterology, Zhongda Hospital, School of Medicine, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, Jiangsu Province, People's Republic of China
| | - Yang Liu
- Department of Gastroenterology, Zhongda Hospital, School of Medicine, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, Jiangsu Province, People's Republic of China
| | - Yadong Feng
- Department of Gastroenterology, Zhongda Hospital, School of Medicine, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, Jiangsu Province, People's Republic of China
| | - Jingwu Dong
- Department of Gastroenterology, Xuyi County People's Hospital, Huaian, 211700, People's Republic of China
| | - Ruihua Shi
- Department of Gastroenterology, Zhongda Hospital, School of Medicine, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, Jiangsu Province, People's Republic of China.
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Li Y, Hu J, Guo D, Ma W, Zhang X, Zhang Z, Lu G, He S. LncRNA SNHG5 promotes the proliferation and cancer stem cell-like properties of HCC by regulating UPF1 and Wnt-signaling pathway. Cancer Gene Ther 2022; 29:1373-1383. [PMID: 35338348 PMCID: PMC9576592 DOI: 10.1038/s41417-022-00456-3] [Citation(s) in RCA: 39] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Revised: 02/10/2022] [Accepted: 03/04/2022] [Indexed: 12/22/2022]
Abstract
The role of long noncoding RNA (lncRNAs) had been demonstrated in different types of cancer, including hepatocellular carcinoma. This study was intended to investigate the role of lncRNA small nucleolar RNA host gene 5 (SNHG5) in HCC proliferation and the liver CSC-like properties. Through functional experiments, we determined that knockdown of SNHG5 repressed HCC cell proliferation and CSC-like properties, while over-expression of SNHG5 promoted cell growth. At the same time, CSC markers (CD44, CD133, and ALDH1) and related transcription factors (OCT4, SOX2, and NANOG) were downregulated when SNHG5 was knocked down. Mechanically, RNA immunoprecipitation (RIP) and RNA pulldown assay showed that SNHG5 regulated the proliferation and CSC-like properties of HCC by binding UPF1. Further investigations showed that expression of critical components of Wnt/β-catenin pathway (β-catenin, TCF4, c-myc, cyclinD1, and c-Jun) were upregulated with depletion of UPF1 in liver CSCs, which were downregulated with depletion of SNHG5. After use of the inhibitor of Wnt/β-catenin pathway, the formation of liver CSCs sphere decreased. Taken together, SNHG5 plays a critical role to promote HCC cell proliferation and cancer stem cell-like properties via UPF1 and Wnt/β-catenin pathway.
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Affiliation(s)
- Yarui Li
- Department of Gastroenterology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, P.R. China
| | - Junbi Hu
- Department of Gastroenterology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, P.R. China
| | - Dan Guo
- Department of Gastroenterology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, P.R. China
| | - Wenhui Ma
- Department of Gastroenterology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, P.R. China
| | - Xu Zhang
- Department of Gastroenterology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, P.R. China
| | - Zhiyong Zhang
- Department of Gastroenterology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, P.R. China
| | - Guifang Lu
- Department of Gastroenterology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, P.R. China
| | - Shuixiang He
- Department of Gastroenterology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, P.R. China.
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28
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Li Y, Wan L, Zhang L, Zhuo Z, Luo X, Cui J, Liu Y, Su F, Tang M, Xiao F. Evaluating the activity of nonsense-mediated RNA decay via Nanopore direct RNA sequencing. Biochem Biophys Res Commun 2022; 621:67-73. [DOI: 10.1016/j.bbrc.2022.06.055] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2022] [Revised: 06/01/2022] [Accepted: 06/18/2022] [Indexed: 11/27/2022]
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29
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Gonzalez Quesada Y, Bonnet-Magnaval F, DesGroseillers L. Phosphomimicry on STAU1 Serine 20 Impairs STAU1 Posttranscriptional Functions and Induces Apoptosis in Human Transformed Cells. Int J Mol Sci 2022; 23:ijms23137344. [PMID: 35806349 PMCID: PMC9266326 DOI: 10.3390/ijms23137344] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Revised: 06/28/2022] [Accepted: 06/29/2022] [Indexed: 12/22/2022] Open
Abstract
Staufen 1 (STAU1) is an RNA-binding protein that is essential in untransformed cells. In cancer cells, it is rather STAU1 overexpression that impairs cell proliferation. In this paper, we show that a modest increase in STAU1 expression in cancer cells triggers apoptosis as early as 12 h post-transfection and impairs proliferation in non-apoptotic cells for several days. Interestingly, a mutation that mimics the phosphorylation of STAU1 serine 20 is sufficient to cause these phenotypes, indicating that serine 20 is at the heart of the molecular mechanism leading to apoptosis. Mechanistically, phosphomimicry on serine 20 alters the ability of STAU1 to regulate translation and the decay of STAU1-bound mRNAs, indicating that the posttranscriptional regulation of mRNAs by STAU1 controls the balance between proliferation and apoptosis. Unexpectedly, the expression of RBD2S20D, the N-terminal 88 amino acids with no RNA-binding activity, is sufficient to induce apoptosis via alteration, in trans, of the posttranscriptional functions of endogenous STAU1. These results suggest that STAU1 is a sensor that controls the balance between cell proliferation and apoptosis, and, therefore, may be considered as a novel therapeutic target against cancer.
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30
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Han Y, Huang Y, Yang Q, Jia L, Zheng Y, Li W. Long non-coding RNA SNHG5 mediates periodontal inflammation through the NF-κB signaling pathway. J Clin Periodontol 2022; 49:1038-1051. [PMID: 35713268 DOI: 10.1111/jcpe.13684] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2022] [Revised: 05/14/2022] [Accepted: 06/12/2022] [Indexed: 11/30/2022]
Abstract
AIM We investigated the role of the long non-coding RNA (lncRNA), small nucleolar RNA host gene 5 (SNHG5), in the pathogenesis of periodontitis. MATERIALS AND METHODS A ligature-induced periodontitis mouse model was established, and gingival tissues from patients with periodontitis and healthy controls were collected. Inflammatory cytokines were detected using qRT-PCR and western blotting analyses. Direct interactions between SNHG5 and p65 were detected by RNA pull-down and RNA immunoprecipitation assays. Micro-computed tomography, hematoxylin and eosin staining, and immunohistochemical staining were used to measure periodontal bone loss. RESULTS SNHG5 expression was downregulated in human and mouse periodontal tissues compared to that in the healthy controls. In vitro experiments demonstrated that SNHG5 significantly ameliorated tumor necrosis factor-α (TNFα)-induced inflammation. Mechanistically, SNHG5 directly binds to the nuclear factor-kappa B (NF-κB) p65 subunit and inhibits its translocation, thereby suppressing the NF-κB signaling pathway activation and reducing the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 inflammasome expression. Locally injecting si-SNHG5 aggravated the periodontal destruction. CONCLUSION This study revealed that SNHG5 mediates periodontal inflammation through the NF-κB signaling pathway, providing a potential therapeutic target for periodontitis treatment. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Yineng Han
- Department of Orthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing, People's Republic of China.,National Center of Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing, China
| | - Yiping Huang
- Department of Orthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing, People's Republic of China.,National Center of Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing, China
| | - Qiaolin Yang
- Department of Orthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing, People's Republic of China.,National Center of Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing, China
| | - Lingfei Jia
- Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing, People's Republic of China.,Central Laboratory, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing, People's Republic of China.,National Center of Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing, China
| | - Yunfei Zheng
- Department of Orthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing, People's Republic of China.,National Center of Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing, China
| | - Weiran Li
- Department of Orthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing, People's Republic of China.,National Center of Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing, China
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31
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Xu Y, Yu X, Sun Z, He Y, Guo W. Roles of lncRNAs Mediating Wnt/β-Catenin Signaling in HCC. Front Oncol 2022; 12:831366. [PMID: 35356220 PMCID: PMC8959654 DOI: 10.3389/fonc.2022.831366] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2021] [Accepted: 02/14/2022] [Indexed: 11/18/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is considered the second most deadly cancer worldwide. Due to the absence of early diagnostic markers and effective therapeutic approaches, distant metastasis and increasing recurrence rates are major difficulties in the clinical treatment of HCC. Further understanding of its pathogenesis has become an urgent goal in HCC research. Recently, abnormal expression of long noncoding RNAs (lncRNAs) was identified as a vital regulator involved in the initiation and development of HCC. Activation of the Wnt/β-catenin pathway has been reported to obviously impact cell proliferation, invasion, and migration of HCC. This article reviews specific interactions, significant mechanisms and molecules related to HCC initiation and progression to provide promising strategies for treatment.
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Affiliation(s)
- Yating Xu
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Open and Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation at Henan Universities, Zhengzhou, China.,Zhengzhou Key Laboratory of Hepatobiliary & Pancreatic Diseases and Organ Transplantation Medicine, Zhengzhou, China
| | - Xiao Yu
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Open and Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation at Henan Universities, Zhengzhou, China.,Zhengzhou Key Laboratory of Hepatobiliary & Pancreatic Diseases and Organ Transplantation Medicine, Zhengzhou, China
| | - Zongzong Sun
- Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yuting He
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Open and Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation at Henan Universities, Zhengzhou, China.,Zhengzhou Key Laboratory of Hepatobiliary & Pancreatic Diseases and Organ Transplantation Medicine, Zhengzhou, China
| | - Wenzhi Guo
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Open and Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation at Henan Universities, Zhengzhou, China.,Zhengzhou Key Laboratory of Hepatobiliary & Pancreatic Diseases and Organ Transplantation Medicine, Zhengzhou, China
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Han Y, Yang Q, Huang Y, Jia L, Zheng Y, Li W. Long non-coding RNA SNHG5 promotes the osteogenic differentiation of bone marrow mesenchymal stem cells via the miR-212-3p/GDF5/SMAD pathway. Stem Cell Res Ther 2022; 13:130. [PMID: 35346361 PMCID: PMC8962127 DOI: 10.1186/s13287-022-02781-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Accepted: 08/23/2021] [Indexed: 01/15/2023] Open
Abstract
Background The treatment of bone loss has posed a challenge to clinicians for decades. Thus, it is of great significance to identify more effective methods for bone regeneration. However, the role and mechanisms of long non-coding RNA small nucleolar RNA host gene 5 (SNHG5) during osteogenic differentiation remain unclear. Methods We investigated the function of SNHG5, Yin Yang 1 (YY1), miR-212-3p and growth differentiation factor 5 (GDF5) in osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs) in vitro and in vivo. Molecular mechanisms were clarified by chromatin immunoprecipitation assay and dual luciferase reporter assay. Results We found SNHG5 expression was upregulated during osteogenesis of hBMSCs. Knockdown of SNHG5 in hBMSCs inhibited osteogenic differentiation while overexpression of SNHG5 promoted osteogenesis. Moreover, YY1 transcription factor directly bound to the promoter region of SNHG5 and regulated SNHG5 expression to promote osteogenesis. Dual luciferase reporter assay confirmed that SNHG5 acted as a miR-212-3p sponge and miR-212-3p directly targeted GDF5 and further activated Smad1/5/8 phosphorylation. miR-212-3p inhibited osteogenic differentiation, while GDF5 promoted osteogenic differentiation of hBMSCs. In addition, calvarial defect experiments showed knockdown of SNHG5 and GDF5 inhibited new bone formation in vivo. Conclusion Our results demonstrated that the novel pathway YY1/SNHG5/miR-212-3p/GDF5/Smad regulates osteogenic differentiation of hBMSCs and may serve as a potential target for the treatment of bone loss. Supplementary Information The online version contains supplementary material available at 10.1186/s13287-022-02781-8.
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Affiliation(s)
- Yineng Han
- Department of Orthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing, 100081, People's Republic of China
| | - Qiaolin Yang
- Department of Orthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing, 100081, People's Republic of China
| | - Yiping Huang
- Department of Orthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing, 100081, People's Republic of China
| | - Lingfei Jia
- Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing, 100081, People's Republic of China.,Central Laboratory, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing, 100081, People's Republic of China
| | - Yunfei Zheng
- Department of Orthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing, 100081, People's Republic of China.
| | - Weiran Li
- Department of Orthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing, 100081, People's Republic of China.
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RBM47/SNHG5/FOXO3 axis activates autophagy and inhibits cell proliferation in papillary thyroid carcinoma. Cell Death Dis 2022; 13:270. [PMID: 35338124 PMCID: PMC8956740 DOI: 10.1038/s41419-022-04728-6] [Citation(s) in RCA: 42] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2021] [Revised: 02/23/2022] [Accepted: 03/11/2022] [Indexed: 02/08/2023]
Abstract
Papillary thyroid carcinoma (PTC) is the main type of thyroid carcinoma. Despite the good prognosis, some PTC patients may deteriorate into more aggressive diseases, leading to poor survival. Molecular technology has been increasingly used in the diagnosis and treatment of thyroid carcinoma. In this study, we identified that RNA Binding Motif Protein 47 (RBM47) was downregulated in PTC tissues and cells, and overexpression of RBM47 could activate autophagy and inhibit proliferation in PTC cells. RBM47 promotes but can not bind directly to Forkhead Box O3 (FOXO3). FOXO3 activates Autophagy Related Gene 3 (ATG3), ATG5, and RBM47 to form a loop and promote autophagy. RBM47 can bind directly to and stabilized lncRNA Small Nucleolar RNA Host Gene 5 (SNHG5) to inhibit PTC cells proliferation and activate autophagy in vitro and in vivo. SNHG5 inhibits ubiquitination and degradation of FOXO3 by recruiting Ubiquitin Specific Peptidase 21 (USP21), then promotes the translocation of FOXO3 from cytoplasm to nucleus. Our study revealed the regulatory mechanism of RBM47/SNHG5/FOXO3 axis on cell proliferation and autophagy in PTC, which may provide valuable insight for the treatment of PTC.
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Non-coding RNAs as emerging regulators and biomarkers in colorectal cancer. Mol Cell Biochem 2022; 477:1817-1828. [PMID: 35332394 DOI: 10.1007/s11010-022-04412-5] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Accepted: 03/10/2022] [Indexed: 11/09/2022]
Abstract
CRC is the third most common cancer occurring worldwide and the second leading cause of cancer deaths. In the year 2020, 1,931,590 new cases of CRC and 935,173 deaths were reported. The last two decades have witnessed an intensive study of noncoding RNAs and their implications in various pathological conditions including cancer. Noncoding RNAs such as miRNAs, tsRNAs, piRNAs, lncRNAs, pseudogenes, and circRNAs have emerged as promising prognostic and diagnostic biomarkers in preclinical studies of cancer. Some of these noncoding RNAs have also been shown as promising therapeutic targets for cancer treatment. In this review, we have discussed the emerging roles of various types of noncoding RNAs in CRC and their future implications in colorectal cancer management and research.
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Long noncoding RNA LUCAT1 enhances the survival and therapeutic effects of mesenchymal stromal cells post-myocardial infarction. MOLECULAR THERAPY - NUCLEIC ACIDS 2022; 27:412-426. [PMID: 35036054 PMCID: PMC8733180 DOI: 10.1016/j.omtn.2021.12.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Accepted: 12/09/2021] [Indexed: 11/25/2022]
Abstract
Mesenchymal stromal cell (MSC) transplantation has been a promising therapeutic strategy for repairing heart tissues post-myocardial infarction (MI). Nevertheless, its therapeutic efficacy remains low, which is mainly ascribed to the low viability of transplanted MSCs. Recently, long noncoding RNAs (lncRNAs) have been reported to participate in diverse physiological and pathological processes, but little is known about their role in MSC survival. Using unbiased transcriptome profiling of hypoxia-preconditioned MSCs (HP-MSCs) and normoxic MSCs (N-MSCs), we identified a lncRNA named lung cancer-associated transcript 1 (LUCAT1) under hypoxia. LUCAT1 knockdown reduced the survival of engrafted MSCs and decreased the MSC-based therapeutic potency, as shown by impaired cardiac function, reduced cardiomyocyte survival, and increased fibrosis post-MI. Conversely, LUCAT1 overexpression had the opposite results. Mechanistically, LUCAT1 bound with and recruited jumonji domain-containing 6 (JMJD6) to the promoter of forkhead box Q1 (FOXQ1), which demethylated FOXQ1 at H4R3me2(s) and H3R2me2(a), thus downregulating Bax expression and upregulating Bcl-2 expression to attenuate MSC apoptosis. Therefore, our findings revealed the protective effects of LUCAT1 on MSC apoptosis and demonstrated that the LUCAT1-mediated JMJD6-FOXQ1 pathway might represent a novel target to potentiate the therapeutic effect of MSC-based therapy for ischemic cardiovascular diseases.
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Yan J, Huang QY, Huang YJ, Wang CS, Liu PX. SPATS2 is positively activated by long noncoding RNA SNHG5 via regulating DNMT3a expression to promote hepatocellular carcinoma progression. PLoS One 2022; 17:e0262262. [PMID: 35077478 PMCID: PMC8789170 DOI: 10.1371/journal.pone.0262262] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Accepted: 12/21/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most prevalent malignant tumors with high mortality worldwide. Spermatogenesis-associated serine-rich 2 (SPATS2) could be a novel diagnostic and prognostic biomarker in HCC. However, the regulatory mechanism of SPATS2 in HCC requires further elucidation. Therefore, the study’s objective was to investigate this process in HCC. In this study, we found that SPATS2 is significantly upregulated in HepG2 cells to promote cell growth and migration. SPATS2 is the target transcript of lncRNA SNHG5. SPATS2 positively affects the proliferation and migration of HepG2 cells caused by the higher expression of SNHG5. Mechanistically, we identified that the elevated of SPATS2 was attributed to SNHG5 related hypomethylation of SPATS2. SNHG5 reduced the expression of DNMT3a to suppress the methylation level of SPATS2. Taken together, our results uncover a novel epigenetic regulatory mechanism of lncRNA SNHG5-DNMT3a axis-related SPATS2 expression underlying HCC progression. This may serve as a novel prognostic marker and a promising therapeutic target for the treatment of HCC.
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Affiliation(s)
- Jia Yan
- College of Life Science, Inner Mongolia University, Hohhot, China
| | - Qing Yu Huang
- College of Life Science, Inner Mongolia University, Hohhot, China
| | - Ya Jun Huang
- College of Life Science, Inner Mongolia University, Hohhot, China
| | - Chang Shan Wang
- College of Life Science, Inner Mongolia University, Hohhot, China
- * E-mail: (CSW); (PXL)
| | - Peng Xia Liu
- College of Life Science, Inner Mongolia University, Hohhot, China
- * E-mail: (CSW); (PXL)
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Guo Q, Dong L, Zhang C, Liu D, Peng P. MicroRNA-363-3p, negatively regulated by long non-coding RNA small nucleolar RNA host gene 5, inhibits tumor progression by targeting Aurora kinase A in colorectal cancer. Bioengineered 2022; 13:5357-5372. [PMID: 35166647 PMCID: PMC8973704 DOI: 10.1080/21655979.2021.2018972] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
MicroRNA-363-3p (miR-363-3p), reportedly, exhibits a tumor-suppressive role in human malignancies. Herein, our research was designed to further explain the functions and molecular mechanisms of miR-363-3p in the progression of colorectal cancer (CRC). With in vitro models, this study found that miR-363-3p was markedly under-expressed in CRC tissues and cells, and its overexpression suppressed the viability, migration, and invasion of CRC cells, and promoted cell apoptosis, whereas inhibiting miR-363-3p expression exhibited an opposite role. Additionally, aurora kinase A (AURKA), capable of counteracting the impacts of miR-363-3p on malignant biological behaviors of CRC cells, was identified as a direct target of miR-363-3p. Besides, miR-363-3p was sponged by long non-coding RNA small nucleolar RNA host gene 5 (SNHG5), which suppressed miR-363-3p expression. This research shows that SNHG5/miR-363-3p/AURKA axis partakes in CRC progression.
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Affiliation(s)
- Qiuyun Guo
- Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan Hubei, China
| | - Lujia Dong
- Department of Gastrointestinal Surgery, Xi'an No. 3 Hospital, the Affiliated Hospital of Northwest University, Xi'an, Shaanxi Province, China
| | - Chenxiao Zhang
- Department of Gastrointestinal Surgery, Xi'an No. 3 Hospital, the Affiliated Hospital of Northwest University, Xi'an, Shaanxi Province, China
| | - Dechun Liu
- Department of Gastrointestinal Surgery, Xi'an No. 3 Hospital, the Affiliated Hospital of Northwest University, Xi'an, Shaanxi Province, China
| | - Ping Peng
- Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan Hubei, China
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Bonnet-Magnaval F, Diallo LH, Brunchault V, Laugero N, Morfoisse F, David F, Roussel E, Nougue M, Zamora A, Marchaud E, Tatin F, Prats AC, Garmy-Susini B, DesGroseillers L, Lacazette E. High Level of Staufen1 Expression Confers Longer Recurrence Free Survival to Non-Small Cell Lung Cancer Patients by Promoting THBS1 mRNA Degradation. Int J Mol Sci 2021; 23:215. [PMID: 35008641 PMCID: PMC8745428 DOI: 10.3390/ijms23010215] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Revised: 12/20/2021] [Accepted: 12/21/2021] [Indexed: 12/12/2022] Open
Abstract
Stau1 is a pluripotent RNA-binding protein that is responsible for the post-transcriptional regulation of a multitude of transcripts. Here, we observed that lung cancer patients with a high Stau1 expression have a longer recurrence free survival. Strikingly, Stau1 did not impair cell proliferation in vitro, but rather cell migration and cell adhesion. In vivo, Stau1 depletion favored tumor progression and metastases development. In addition, Stau1 depletion strongly impaired vessel maturation. Among a panel of candidate genes, we specifically identified the mRNA encoding the cell adhesion molecule Thrombospondin 1 (THBS1) as a new target for Staufen-mediated mRNA decay. Altogether, our results suggest that regulation of THBS1 expression by Stau1 may be a key process involved in lung cancer progression.
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Affiliation(s)
- Florence Bonnet-Magnaval
- U1297-Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse, F-31432 Toulouse, France; (F.B.-M.); (L.H.D.); (V.B.); (N.L.); (F.M.); (F.D.); (E.R.); (M.N.); (A.Z.); (E.M.); (F.T.); (B.G.-S.)
- Département de Biochimie Et Médecine Moléculaire, Faculté de Médecine, Université de Montréal, 2900 Édouard Montpetit Montréal, Montreal, QC H3T 1J4, Canada;
| | - Leïla Halidou Diallo
- U1297-Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse, F-31432 Toulouse, France; (F.B.-M.); (L.H.D.); (V.B.); (N.L.); (F.M.); (F.D.); (E.R.); (M.N.); (A.Z.); (E.M.); (F.T.); (B.G.-S.)
| | - Valérie Brunchault
- U1297-Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse, F-31432 Toulouse, France; (F.B.-M.); (L.H.D.); (V.B.); (N.L.); (F.M.); (F.D.); (E.R.); (M.N.); (A.Z.); (E.M.); (F.T.); (B.G.-S.)
| | - Nathalie Laugero
- U1297-Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse, F-31432 Toulouse, France; (F.B.-M.); (L.H.D.); (V.B.); (N.L.); (F.M.); (F.D.); (E.R.); (M.N.); (A.Z.); (E.M.); (F.T.); (B.G.-S.)
| | - Florent Morfoisse
- U1297-Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse, F-31432 Toulouse, France; (F.B.-M.); (L.H.D.); (V.B.); (N.L.); (F.M.); (F.D.); (E.R.); (M.N.); (A.Z.); (E.M.); (F.T.); (B.G.-S.)
| | - Florian David
- U1297-Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse, F-31432 Toulouse, France; (F.B.-M.); (L.H.D.); (V.B.); (N.L.); (F.M.); (F.D.); (E.R.); (M.N.); (A.Z.); (E.M.); (F.T.); (B.G.-S.)
| | - Emilie Roussel
- U1297-Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse, F-31432 Toulouse, France; (F.B.-M.); (L.H.D.); (V.B.); (N.L.); (F.M.); (F.D.); (E.R.); (M.N.); (A.Z.); (E.M.); (F.T.); (B.G.-S.)
| | - Manon Nougue
- U1297-Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse, F-31432 Toulouse, France; (F.B.-M.); (L.H.D.); (V.B.); (N.L.); (F.M.); (F.D.); (E.R.); (M.N.); (A.Z.); (E.M.); (F.T.); (B.G.-S.)
| | - Audrey Zamora
- U1297-Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse, F-31432 Toulouse, France; (F.B.-M.); (L.H.D.); (V.B.); (N.L.); (F.M.); (F.D.); (E.R.); (M.N.); (A.Z.); (E.M.); (F.T.); (B.G.-S.)
| | - Emmanuelle Marchaud
- U1297-Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse, F-31432 Toulouse, France; (F.B.-M.); (L.H.D.); (V.B.); (N.L.); (F.M.); (F.D.); (E.R.); (M.N.); (A.Z.); (E.M.); (F.T.); (B.G.-S.)
| | - Florence Tatin
- U1297-Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse, F-31432 Toulouse, France; (F.B.-M.); (L.H.D.); (V.B.); (N.L.); (F.M.); (F.D.); (E.R.); (M.N.); (A.Z.); (E.M.); (F.T.); (B.G.-S.)
| | - Anne-Catherine Prats
- U1297-Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse, F-31432 Toulouse, France; (F.B.-M.); (L.H.D.); (V.B.); (N.L.); (F.M.); (F.D.); (E.R.); (M.N.); (A.Z.); (E.M.); (F.T.); (B.G.-S.)
| | - Barbara Garmy-Susini
- U1297-Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse, F-31432 Toulouse, France; (F.B.-M.); (L.H.D.); (V.B.); (N.L.); (F.M.); (F.D.); (E.R.); (M.N.); (A.Z.); (E.M.); (F.T.); (B.G.-S.)
| | - Luc DesGroseillers
- Département de Biochimie Et Médecine Moléculaire, Faculté de Médecine, Université de Montréal, 2900 Édouard Montpetit Montréal, Montreal, QC H3T 1J4, Canada;
| | - Eric Lacazette
- U1297-Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse, F-31432 Toulouse, France; (F.B.-M.); (L.H.D.); (V.B.); (N.L.); (F.M.); (F.D.); (E.R.); (M.N.); (A.Z.); (E.M.); (F.T.); (B.G.-S.)
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Lu S, Ding X, Wang Y, Hu X, Sun T, Wei M, Wang X, Wu H. The Relationship Between the Network of Non-coding RNAs-Molecular Targets and N6-Methyladenosine Modification in Colorectal Cancer. Front Cell Dev Biol 2021; 9:772542. [PMID: 34938735 PMCID: PMC8685436 DOI: 10.3389/fcell.2021.772542] [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: 09/08/2021] [Accepted: 11/11/2021] [Indexed: 12/11/2022] Open
Abstract
Recent accumulating researches implicate that non-coding RNAs (ncRNAs) including microRNA (miRNA), circular RNA (circRNA), and long non-coding RNA (lncRNAs) play crucial roles in colorectal cancer (CRC) initiation and development. Notably, N6-methyladenosine (m6A) methylation, the critical posttranscriptional modulators, exerts various functions in ncRNA metabolism such as stability and degradation. However, the interaction regulation network among ncRNAs and the interplay with m6A-related regulators has not been well documented, particularly in CRC. Here, we summarize the interaction networks and sub-networks of ncRNAs in CRC based on a data-driven approach from the publications (IF > 6) in the last quinquennium (2016–2021). Further, we extend the regulatory pattern between the core m6A regulators and m6A-related ncRNAs in the context of CRC metastasis and progression. Thus, our review will highlight the clinical potential of ncRNAs and m6A modifiers as promising biomarkers and therapeutic targets for improving the diagnostic precision and treatment of CRC.
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Affiliation(s)
- Senxu Lu
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, China.,Liaoning Key Laboratory of Molecular Targeted Anti-tumor Drug Development and Evaluation, Liaoning Cancer Immune Peptide Drug Engineering Technology Research Center, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, Shenyang, China
| | - Xiangyu Ding
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, China.,Liaoning Key Laboratory of Molecular Targeted Anti-tumor Drug Development and Evaluation, Liaoning Cancer Immune Peptide Drug Engineering Technology Research Center, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, Shenyang, China
| | - Yuanhe Wang
- Department of Medical Oncology, Cancer Hospital of China Medical University, Shenyang, China
| | - Xiaoyun Hu
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, China.,Liaoning Key Laboratory of Molecular Targeted Anti-tumor Drug Development and Evaluation, Liaoning Cancer Immune Peptide Drug Engineering Technology Research Center, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, Shenyang, China
| | - Tong Sun
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, China.,Liaoning Key Laboratory of Molecular Targeted Anti-tumor Drug Development and Evaluation, Liaoning Cancer Immune Peptide Drug Engineering Technology Research Center, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, Shenyang, China
| | - Minjie Wei
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, China.,Liaoning Key Laboratory of Molecular Targeted Anti-tumor Drug Development and Evaluation, Liaoning Cancer Immune Peptide Drug Engineering Technology Research Center, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, Shenyang, China.,Shenyang Kangwei Medical Laboratory Analysis Co. Ltd., Liaoning, China
| | - Xiaobin Wang
- Center of Reproductive Medicine, Shengjing Hospital of China Medical University, Shenyang, China
| | - Huizhe Wu
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, China.,Liaoning Key Laboratory of Molecular Targeted Anti-tumor Drug Development and Evaluation, Liaoning Cancer Immune Peptide Drug Engineering Technology Research Center, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, Shenyang, China
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Almasi S, Jasmin BJ. The multifunctional RNA-binding protein Staufen1: an emerging regulator of oncogenesis through its various roles in key cellular events. Cell Mol Life Sci 2021; 78:7145-7160. [PMID: 34633481 PMCID: PMC8629789 DOI: 10.1007/s00018-021-03965-w] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2021] [Revised: 09/19/2021] [Accepted: 09/29/2021] [Indexed: 12/19/2022]
Abstract
The double-stranded multifunctional RNA-binding protein (dsRBP) Staufen was initially discovered in insects as a regulator of mRNA localization. Later, its mammalian orthologs have been described in different organisms, including humans. Two human orthologues of Staufen, named Staufen1 (STAU1) and Staufen2 (STAU2), share some structural and functional similarities. However, given their different spatio-temporal expression patterns, each of these orthologues plays distinct roles in cells. In the current review, we focus on the role of STAU1 in cell functions and cancer development. Since its discovery, STAU1 has mostly been studied for its involvement in various aspects of RNA metabolism. Given the pivotal role of RNA metabolism within cells, recent studies have explored the mechanistic impact of STAU1 in a wide variety of cell functions ranging from cell growth to cell death, as well as in various disease states. In particular, there has been increasing attention on the role of STAU1 in neuromuscular disorders, neurodegeneration, and cancer. Here, we provide an overview of the current knowledge on the role of STAU1 in RNA metabolism and cell functions. We also highlight the link between STAU1-mediated control of cellular functions and cancer development, progression, and treatment. Hence, our review emphasizes the potential of STAU1 as a novel biomarker and therapeutic target for cancer diagnosis and treatment, respectively.
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Affiliation(s)
- Shekoufeh Almasi
- Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, K1H 8M5, Canada
| | - Bernard J Jasmin
- Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, K1H 8M5, Canada.
- The Eric J. Poulin Centre for Neuromuscular Diseases, Faculty of Medicine, University of Ottawa, Ottawa, K1H 8M5, Canada.
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Zhang L, Tan W, Song X, Wang S, Tang L, Chen Y, Yu H, Jiang P, Liu J. Methylprednisolone Attenuates Lipopolysaccharide-Induced Sepsis by Modulating the Small Nucleolar RNA Host Gene 5/Copine 1 Pathway. DNA Cell Biol 2021; 40:1396-1406. [PMID: 34767734 DOI: 10.1089/dna.2021.0376] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Sepsis has become a major public health problem worldwide. Methylprednisolone sodium succinate (MP) is a commonly used drug to prevent inflammation. However, the role and underlying mechanism of MP in sepsis remain vague. MP inhibited the lipopolysaccharide (LPS)-induced production of tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-17 and suppressed cell growth in alveolar type II epithelial cells (ATII cells). Small nucleolar RNA host gene 5 (SNHG5) expression was inhibited by LPS and restored by MP. Upregulation of SNHG5 inhibited the cellular role of LPS in ATII cells, and further, downregulation of SNHG5 inhibited the cellular role of MP in ATII cells under LPS conditions. SNHG5 elevated the expression of Copine 1 (CPNE1) by enhancing the mRNA stability of CPNE1. Increasing CPNE1 expression restored the silenced SNHG5-induced inhibitor role of MP in ATII cells under LPS conditions. Finally, MP attenuated lung injury and TNF-α and IL-17 secretion in an LPS-induced sepsis mouse model. Overall, this study investigated the mechanism underlying the effect of MP treatment in sepsis and, for the first time, revealed the important role of the SNHG5/CPNE1 pathway in the development and treatment of sepsis and the potential to serve as a diagnostic and therapeutic target for sepsis.
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Affiliation(s)
- Li Zhang
- Department of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
| | - Wei Tan
- Department of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
| | - Xinmiao Song
- Department of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
| | - Shanmei Wang
- Department of Emergency, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
| | - Liang Tang
- Department of Central Laboratory, and Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
| | - Yu Chen
- Department of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
| | - Hanqing Yu
- Department of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
| | - Ping Jiang
- Department of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
| | - Jinming Liu
- Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
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Suo RY, Wang ZY, Wang JS, Zhang GJ, Zhang J. Role of long non-coding RNA in regulating polarization of gastric cancer macrophages. Shijie Huaren Xiaohua Zazhi 2021; 29:1096-1101. [DOI: 10.11569/wcjd.v29.i19.1096] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Tumor-associated macrophages (TAMs) are an important part of the tumor microenvironment. They are distributed in tumor tissues and distant metastatic sites, and are related to tumor progression and prognosis. TAMs M2 can promote tumor biological processes such as tumor proliferation, invasion, and metastasis, and inhibit apoptosis, and are obviously related to the poor prognosis of tumor patients. In recent years, the role of long non-coding RNAs (lncRNAs) in regulating the polarization of macrophages has gradually been revealed, which can affect the occurrence and development of tumors by adjusting the polarization of macrophages. Studies have shown that lncRNAs play an important role in the polarization process of gastric cancer macrophages. This article summarizes the related research reports, hoping to provide ideas for studies that interfere with the polarization process of TAMs to inhibit tumor progression.
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Affiliation(s)
- Rui-Yang Suo
- Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China,Xi'an Jiaotong University Health Science Center, Xi'an 710061, China
| | - Zhi-Yu Wang
- Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China,Xi'an Jiaotong University Health Science Center, Xi'an 710061, China
| | - Jian-Sheng Wang
- Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China
| | - Guang-Jian Zhang
- Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China
| | - Jia Zhang
- Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China
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Wang X, Liu F, Zhang N, Ma L. Long Non-Coding RNA, Small Nucleolar RNA Host Gene 5, Inhibits the Oxidized Low-Density Lipoprotein Induced Vascular Endothelial Cell Injury by Targeting miR-26a-5p. J BIOMATER TISS ENG 2021. [DOI: 10.1166/jbt.2021.2774] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
Atherosclerosis is the major cause of cardiovascular disease, and endothelial cell injury is the primary atherogenic factor. Long non-coding RNAs (lncRNAs) are increasingly implicated as critical regulators of disease progression. Still, the role of lncRNA in endothelial cell injury
is largely unknown. This issue was explored in control, ox-LDL stimulated, ox-LDL stimulated+transfected negative control vector, and ox-LDL stimulated+SNHG5 overexpression vector EA. hy926 cells. Quantitative real-time PCR used to assess the expression of SNHG5 and miR-26a-5p. Flow cytometry
was used to evaluate cell apoptosis. Activity or concentration of SOD, MDA, CAT, and reactive oxygen species (ROS) was measured to assess oxidative stress. Western blotting was used to examine protein-level expression of cleaved Caspase-3, cleaved Caspase-9, and cyt-c in cytoplasm and mitochondria.
Potential binding sites between SNHG5 and miR-26a-5p were predicted using Starbase software, and dual-luciferase reporter assays were used to identify target relationships. SNHG5 expression in cells following ox-LDL treatment was downregulated in EA. hy926 cells. Ox-LDL treatment promotes
apoptosis, and increased C-Caspase-3, C-Caspase-9, and cytoplasmic cyt-c protein levels. MDA concentration and ROS activity were increased, while the activity of SOD and CAT was decreased. Transfection with SNHG5 reversed the effects of ox-LDL on cell apoptosis and oxidative stress. SNHG5
targeted miR-26a-5p and regulated its expression. miR-26a-5p mimics reversed SNHG5 modulation of apoptosis and oxidative stress. lncRNA SNHG5 targets to miR-26a-5p to regulate vascular endothelial cell injury induced by ox-LDL.
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Affiliation(s)
- Xiaoli Wang
- Department of Medical, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, Guangdong, PR China
| | - Fen Liu
- Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, Guangdong, PR China
| | - Neng Zhang
- Department of Cardiovascular Medicine, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, Guangdong, PR China
| | - Li Ma
- Department of Cardiovascular Medicine, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, Guangdong, PR China
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Liang H, Wang J, Zhang P, Yang W, Yang Y, Zhi Y, Wu W, Dong X. Long Non-Coding RNA Duxap8 Facilitates Cell Proliferation and Induces Apoptosis in Colorectal Cancer via miR-519b/ZNF277 Axis. Onco Targets Ther 2021; 14:4693-4703. [PMID: 34511937 PMCID: PMC8420781 DOI: 10.2147/ott.s301233] [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: 04/14/2021] [Accepted: 07/23/2021] [Indexed: 11/26/2022] Open
Abstract
Introduction Long non-coding RNAs (LncRNAs) play a critical role in development and progression of various cancers. More and more researchers pay attention to the effect of lncRNA on regulating the cancer. However, the function and mechanism of Duxap8 in colorectal cancer have not been studied. Methods Reverse transcription quantitative PCR (RT-qPCR), cell counting kit-8 (CCK-8), 5-ethynyl-20-deoxyuridine (EdU), colony formation assay, flow cytometry, TdT-mediated dUTP nick-end labeling (TUNEL), Western blot, hematoxylin-eosin staining (HE), in situ hybridization (ISH) analysis, immunohistochemistry (IHC) and tumor transplantation experiment were performed to investigate the function and mechanism of Duxap8 in colorectal cancer. Results We found that the expression level of Duxap8 in colorectal cancer was closely correlated with tumor size (P = 0.024), tumor depth (P = 0.035) and lymphatic invasion (P =0.067) among 50 colorectal cancer patients. Then, we proved that the expression level of Duxap8 was significantly increased in human colorectal cancer tissues and cell lines. Functionally, Duxap8 knockdown inhibited the proliferation and induced the apoptosis of colorectal cancer cells, while Duxap8 overexpression facilitated the proliferation and suppressed the apoptosis in colorectal cancer in vitro. Moreover, knockdown of Duxap8 inhibited the size and weight of tumors in mice injected with colorectal cancer cells, overexpression of Duxap8 promoted the growth of colorectal cancer cells in vivo. Mechanically, we found that Duxap8 was principally located in the cytoplasm. Furthermore, Duxap8 functioned as a competing endogenous RNA to induce the development and progression of colorectal cancer through sponging miR-519b-3p to upregulate ZNF277. Discussion Taken together, our results demonstrated that Duxap8 enhanced the expression level of ZEB1 to promote via competing for miR-519b-3p, which might be a promising molecular therapeutic target of colorectal cancer.
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Affiliation(s)
- Hailiang Liang
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, 215006, People's Republic of China
| | - Jin Wang
- Department of General Surgery, Suzhou Dushu Lake Hospital (Dushu Lake Hospital Affiliated to Soochow University), Suzhou, 215006, People's Republic of China
| | - Peng Zhang
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, 215006, People's Republic of China
| | - Wei Yang
- Department of General Surgery, The Affiliated Hospital of Yangzhou University, Yangzhou, 225000, People's Republic of China
| | - Yang Yang
- Department of Anesthesiology, The Affiliated Hospital of Yangzhou University, Yangzhou, 225000, People's Republic of China
| | - Yin Zhi
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, 215006, People's Republic of China
| | - Wei Wu
- Department of General Surgery, The Affiliated Hospital of Yangzhou University, Yangzhou, 225000, People's Republic of China
| | - Xiaoqiang Dong
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, 215006, People's Republic of China
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Barik GK, Sahay O, Behera A, Naik D, Kalita B. Keep your eyes peeled for long noncoding RNAs: Explaining their boundless role in cancer metastasis, drug resistance, and clinical application. Biochim Biophys Acta Rev Cancer 2021; 1876:188612. [PMID: 34391844 DOI: 10.1016/j.bbcan.2021.188612] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2021] [Revised: 08/07/2021] [Accepted: 08/08/2021] [Indexed: 12/12/2022]
Abstract
Cancer metastasis and drug resistance are two major obstacles in the treatment of cancer and therefore, the leading cause of cancer-associated mortalities worldwide. Hence, an in-depth understanding of these processes and identification of the underlying key players could help design a better therapeutic regimen to treat cancer. Earlier thought to be merely transcriptional junk and having passive or secondary function, recent advances in the genomic research have unravelled that long noncoding RNAs (lncRNAs) play pivotal roles in diverse physiological as well as pathological processes including cancer metastasis and drug resistance. LncRNAs can regulate various steps of the complex metastatic cascade such as epithelial-mesenchymal transition (EMT), invasion, migration and metastatic colonization, and also affect the sensitivity of cancer cells to various chemotherapeutic drugs. A substantial body of literature for more than a decade of research evince that lncRNAs can regulate gene expression at different levels such as epigenetic, transcriptional, posttranscriptional, translational and posttranslational levels, depending on their subcellular localization and through their ability to interact with DNA, RNA and proteins. In this review, we mainly focus on how lncRNAs affect cancer metastasis by modulating expression of key metastasis-associated genes at various levels of gene regulation. We also discuss how lncRNAs confer cancer cells either sensitivity or resistance to various chemo-therapeutic drugs via different mechanisms. Finally, we highlight the immense potential of lncRNAs as prognostic and diagnostic biomarkers as well as therapeutic targets in cancer.
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Affiliation(s)
- Ganesh Kumar Barik
- Cancer Biology Division, National Centre for Cell Science, Savitribai Phule Pune University, Ganeshkhind Road, Pune, Maharashtra 411007, India
| | - Osheen Sahay
- Proteomics Laboratory, National Centre for Cell Science, Savitribai Phule Pune University, Ganeshkhind Road, Pune, Maharashtra 411007, India
| | - Abhayananda Behera
- Department of Animal Biology, School of Life Sciences, University of Hyderabad, Hyderabad 500046, India
| | - Debasmita Naik
- Department of Animal Biology, School of Life Sciences, University of Hyderabad, Hyderabad 500046, India
| | - Bhargab Kalita
- Proteomics Laboratory, National Centre for Cell Science, Savitribai Phule Pune University, Ganeshkhind Road, Pune, Maharashtra 411007, India.
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Li H, Xuan J, Zhang W, An Z, Fan X, Lu M, Tian Y. Long non-coding RNA SNHG5 regulates ulcerative colitis via microRNA-375 / Janus kinase-2 axis. Bioengineered 2021; 12:4150-4158. [PMID: 34334085 PMCID: PMC8806617 DOI: 10.1080/21655979.2021.1953219] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
Ulcerative colitis (UC) is an intestinal inflammatory disorder. Long non-coding RNAs (lncRNAs) are collectively involved in UC. This study is designed to explore the roles of lncRNA (small nucleolar RNA host gene 5) SNHG5 in UC. Gene or microRNA (miRNA) expression was detected using RT-qPCR and western blot, respectively. Cellular functions were analyzed by cell counting kit 8 (CCK8), 5-ethynyl-2'-deoxyuridine (EdU) assay, flow cytometry, and the terminal deoxyribonucleotidyl transferase (TDT)-mediated dUTP-digoxigenin nick end labeling (TUNEL) assays. Lactate dehydrogenase (LDH) content was determined by a cell cytotoxicity assay. The interactions between miR-375 and SNHG5 or Janus kinase-2 (JAK2) were verified by a luciferase reporter assay. SNHG5 was up-regulated in intestinal mucosa tissues of UC patients as well as tumor necrosis factor alpha-treated (TNF-α-treated) young adult mouse colon (YAMC) cells. Down-regulated SNHG5 promoted cell proliferation and inhibited apoptosis of YAMC cells. miR-375 was verified to be a target of SNHG5 and was suppressed by TNF-α treatment in YAMC cells. Over-expression of miR-375 restored YAMC cellular functions. Additionally, miR-375 targeted JAK2, which was up-regulated by TNF-α treated YAMC cells. Up-regulation of JAK2 induced the dysfunction of YAMC cells. Knockdown of SNHG5 promoted the proliferation and suppressed the apoptosis of YAMC cells via regulating miR-375/JAK2 axis. Therefore, knockdown of SNHG5 may be a promising therapy for UC.
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Affiliation(s)
- Hui Li
- Department of Gastroenterology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Ji Xuan
- Department of Gastroenterology, Jinling Hospital, Nanjing, China
| | - Wei Zhang
- Department of Gastroenterology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Zhentao An
- Department of Gastroenterology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Xinyu Fan
- Department of Preventive Treatment, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Min Lu
- Department of Gastroenterology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Yaozhou Tian
- Department of Gastroenterology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
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Huang GW, Chen QQ, Ma CC, Xie LH, Gu J. linc01305 promotes metastasis and proliferation of esophageal squamous cell carcinoma through interacting with IGF2BP2 and IGF2BP3 to stabilize HTR3A mRNA. Int J Biochem Cell Biol 2021; 136:106015. [PMID: 34022433 DOI: 10.1016/j.biocel.2021.106015] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2021] [Revised: 05/08/2021] [Accepted: 05/12/2021] [Indexed: 02/05/2023]
Abstract
Evidence shows that long noncoding RNAs (lncRNAs) modulate mRNAs of multiple genes by post-transcriptional regulation. However, in esophageal squamous cell carcinoma, lncRNAs involvement in post-transcriptional regulation of mRNAs have been rarely reported. In this study, we investigated a novel mechanism of linc01305 promoting metastasis and proliferation of ESCC. The results for real-time quantitative reverse transcription PCR (qRT-PCR) and fluorescence in situ hybridization showed that linc01305 was highly expressed and predominantly located in cytoplasm of human esophageal cancer cells. Transwell and colony formation assays confirmed that linc01305 promoted migration and proliferation of esophageal cancer cells. RNA-seq, linc01305 pulldown, mass spectrometry, RNA immunoprecipitation and mRNA stability assays demonstrated that linc01305 stabilized mRNA of target gene HTR3A through interacting with IGF2BP2 and IGF2BP3. Taken together, our data unveils a novel mechanism in which cytoplasmic linc01305 stabilizes HTR3A mRNA through interacting with IGF2BP2 and IGF2BP3 and thereby promotes metastasis and proliferation of ESCC.
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MESH Headings
- Apoptosis
- Biomarkers, Tumor/genetics
- Biomarkers, Tumor/metabolism
- Cell Movement
- Cell Proliferation
- Epithelial-Mesenchymal Transition
- Esophageal Neoplasms/genetics
- Esophageal Neoplasms/metabolism
- Esophageal Neoplasms/pathology
- Esophageal Squamous Cell Carcinoma/genetics
- Esophageal Squamous Cell Carcinoma/metabolism
- Esophageal Squamous Cell Carcinoma/secondary
- Gene Expression Regulation, Neoplastic
- Humans
- Prognosis
- RNA, Long Noncoding/genetics
- RNA-Binding Proteins/genetics
- RNA-Binding Proteins/metabolism
- Receptors, Serotonin, 5-HT3/chemistry
- Receptors, Serotonin, 5-HT3/genetics
- Receptors, Serotonin, 5-HT3/metabolism
- Survival Rate
- Tumor Cells, Cultured
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Affiliation(s)
- Guo-Wei Huang
- Department of Pathology, Shantou University Medical College, Shantou, Guangdong, 515041, PR China; Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Shantou University Medical College, Shantou, Guangdong, 515041, PR China
| | - Qian-Qian Chen
- Department of Pathology, Shantou University Medical College, Shantou, Guangdong, 515041, PR China; Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Shantou University Medical College, Shantou, Guangdong, 515041, PR China
| | - Chang-Chun Ma
- Department of Radiation Oncology, Cancer Hospital of Shantou University Medical College, Shantou, 515031, Guangdong Province, PR China
| | - Ling-Hui Xie
- Department of Pathology, Shantou University Medical College, Shantou, Guangdong, 515041, PR China; Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Shantou University Medical College, Shantou, Guangdong, 515041, PR China
| | - Jiang Gu
- Department of Pathology, Shantou University Medical College, Shantou, Guangdong, 515041, PR China; Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Shantou University Medical College, Shantou, Guangdong, 515041, PR China.
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Zhao L, Jiang L, Zhang M, Zhang Q, Guan Q, Li Y, He M, Zhang J, Wei M. NF-κB-activated SPRY4-IT1 promotes cancer cell metastasis by downregulating TCEB1 mRNA via Staufen1-mediated mRNA decay. Oncogene 2021; 40:4919-4929. [PMID: 34163032 PMCID: PMC8321898 DOI: 10.1038/s41388-021-01900-8] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Revised: 05/10/2021] [Accepted: 06/08/2021] [Indexed: 01/09/2023]
Abstract
Previous study demonstrated that most long non-coding RNAs (lncRNAs) function as competing endogenous RNAs or molecular sponges to negatively modulate miRNA and regulate tumor development. However, the molecular mechanisms of lncRNAs in cancer are not fully understood. Our study describes the role of the lncRNA SPRY4 intronic transcript 1 (SPRY4-IT1) in cancer metastasis by mechanisms related to Staufen1 (STAU1)-mediated mRNA decay (SMD). Briefly, we found that, high SPRY4-IT1 expression was associated with aggressiveness and poor outcome in human colorectal, breast and ovarian cancer tissues. In addition, functional assays revealed that SPRY4-IT1 significantly promoted colorectal, breast and ovarian cancer metastasis in vitro and in vivo. Mechanistically, microarray analyses identified several differentially-expressed genes upon SPRY4-IT1 overexpression in HCT 116 colorectal cancer cells. Among them, the 3'-UTR of transcription elongation factor B subunit 1 (TCEB1) mRNA can base-pair with the Alu element in the 3'-UTR of SPRY4-IT1. Moreover, SPRY4-IT1 was found to bind STAU1, promote STAU1 recruitment to the 3'-UTR of TCEB1 mRNA, and affect TCEB1 mRNA stability and expression, resulting in hypoxia-inducible factor 1α (HIF-1α) upregulation, and thereby affecting cancer cell metastasis. In addition, STAU1 depletion abrogated TCEB1 SMD and alleviated the pro-metastatic effect of SPRY4-IT1 overexpression. Significantly, we revealed that SPRY4-IT1 is also transactivated by NF-κB/p65, which activates SPRY4-IT1 to inhibit TCEB1 expression, and subsequently upregulate HIF-1α. In conclusion, our results highlight a novel mechanism of cytoplasmic lncRNA SPRY4-IT1 in which SPRY4-IT1 affecting TCEB1 mRNA stability via STAU1-mediated degradation during cancer metastasis.
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Affiliation(s)
- Lin Zhao
- Department of Pharmacology, School of Pharmacy, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang City, 110122, Liaoning, China
- Liaoning Key Laboratory of molecular targeted anti-tumor drug development and evaluation, China Medical University No.77 Puhe Road, Shenyang North New Area, Shenyang City, 110122, Liaoning, China
| | - Longyang Jiang
- Department of Pharmacology, School of Pharmacy, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang City, 110122, Liaoning, China
- Liaoning Key Laboratory of molecular targeted anti-tumor drug development and evaluation, China Medical University No.77 Puhe Road, Shenyang North New Area, Shenyang City, 110122, Liaoning, China
| | - Ming Zhang
- Department of Pharmacology, School of Pharmacy, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang City, 110122, Liaoning, China
- Liaoning Key Laboratory of molecular targeted anti-tumor drug development and evaluation, China Medical University No.77 Puhe Road, Shenyang North New Area, Shenyang City, 110122, Liaoning, China
| | - Qiang Zhang
- Department of Pharmacology, School of Pharmacy, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang City, 110122, Liaoning, China
- Liaoning Key Laboratory of molecular targeted anti-tumor drug development and evaluation, China Medical University No.77 Puhe Road, Shenyang North New Area, Shenyang City, 110122, Liaoning, China
| | - Qiutong Guan
- Department of Pharmacology, School of Pharmacy, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang City, 110122, Liaoning, China
- Liaoning Key Laboratory of molecular targeted anti-tumor drug development and evaluation, China Medical University No.77 Puhe Road, Shenyang North New Area, Shenyang City, 110122, Liaoning, China
| | - Yalun Li
- Department of Anorectal Surgery, The First Hospital of China Medical University, Shenyang, China
| | - Miao He
- Department of Pharmacology, School of Pharmacy, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang City, 110122, Liaoning, China
- Liaoning Key Laboratory of molecular targeted anti-tumor drug development and evaluation, China Medical University No.77 Puhe Road, Shenyang North New Area, Shenyang City, 110122, Liaoning, China
| | - Jingdong Zhang
- Medical Oncology Department of Gastrointestinal Cancer, Liaoning Cancer Hospital & Institute, Cancer Hospital of China Medical University, Shenyang, China.
| | - Minjie Wei
- Department of Pharmacology, School of Pharmacy, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang City, 110122, Liaoning, China.
- Liaoning Key Laboratory of molecular targeted anti-tumor drug development and evaluation, China Medical University No.77 Puhe Road, Shenyang North New Area, Shenyang City, 110122, Liaoning, China.
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Wei S, Sun S, Zhou X, Zhang C, Li X, Dai S, Wang Y, Zhao L, Shan B. SNHG5 inhibits the progression of EMT through the ubiquitin-degradation of MTA2 in oesophageal cancer. Carcinogenesis 2021; 42:315-326. [PMID: 33095847 DOI: 10.1093/carcin/bgaa110] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2020] [Revised: 09/24/2020] [Accepted: 10/21/2020] [Indexed: 01/06/2023] Open
Abstract
A substantial fraction of transcripts are known as long noncoding RNAs (lncRNAs), and these transcripts play pivotal roles in the development of cancer. However, little information has been published regarding the functions of lncRNAs in oesophageal squamous cell carcinoma (ESCC) and the underlying mechanisms. In our previous studies, we demonstrated that small nucleolar RNA host gene 5 (SNHG5), a known lncRNA, is dysregulated in gastric cancer (GC). In this study, we explored the expression and function of SNHG5 in development of ESCC. SNHG5 was found to be downregulated in human ESCC tissues and cell lines, and this downregulation was associated with cancer progression, clinical outcomes and survival rates of ESCC patients. Furthermore, we also found that overexpression of SNHG5 significantly inhibited the proliferation, migration and invasion of ESCC cells in vivo and in vitro. Notably, we found that metastasis-associated protein 2 (MTA2) was pulled down by SNHG5 in ESCC cells using RNA pulldown assay. We also found that SNHG5 reversed the epithelial-mesenchymal transition by interacting with MTA2. In addition, overexpression of SNHG5 downregulated the transcription of MTA2 and caused its ubiquitin-mediated degradation. Thus, overexpression of MTA2 partially abrogated the effect of SNHG5 in ESCC cell lines. Furthermore, we found that MTA2 mRNA expression was significantly elevated in ESCC specimens, and a negative correlation between SNHG5 and MTA2 expression was detected. Overall, this study demonstrated, for the first time, that SNHG5-regulated MTA2 functions as an important player in the progression of ESCC and provide a new potential therapeutic strategy for ESCC.
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Affiliation(s)
- Sisi Wei
- Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China
| | - Shiping Sun
- Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China.,Blood Transfusion Department, Affiliated Hospital of Chengde Medical University, Chengde, Hebei Province, China
| | - Xinliang Zhou
- Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China
| | - Cong Zhang
- Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China
| | - Xiaoya Li
- Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China
| | - Suli Dai
- Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China
| | - Yaojie Wang
- Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China
| | - Lianmei Zhao
- Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China
| | - Baoen Shan
- Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China
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Wang K, Li Y, Wang J, Chen R, Li J. A novel 12-gene signature as independent prognostic model in stage IA and IB lung squamous cell carcinoma patients. Clin Transl Oncol 2021; 23:2368-2381. [PMID: 34028782 DOI: 10.1007/s12094-021-02638-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Accepted: 05/06/2021] [Indexed: 12/25/2022]
Abstract
BACKGROUND There is currently no formal consensus on the administration of adjuvant chemotherapy to stage I lung squamous cell carcinoma (LUSC) patients despite the poor prognosis. The side effects of adjuvant chemotherapy need to be balanced against the risk of tumour recurrence. Prognostic markers are thus needed to identify those at higher risks and recommend individualised treatment regimens. METHODS Clinical and sequencing data of stage I patients were retrieved from the Lung Squamous Cell Carcinoma project of the Cancer Genome Atlas (TCGA) and three tissue microarray datasets. In a novel K-resample gene selection algorithm, gene-wise Cox proportional hazard regressions were repeated for 50 iterations with random resamples from the TCGA training dataset. The top 200 genes with the best predictive power for survival were chosen to undergo an L1-penalised Cox regression for further gene selection. RESULTS A total of 602 samples of LUSC were included, of which 42.2% came from female patients, 45.3% were stage IA cancer. From an initial pool of 11,212 genes in the TCGA training dataset, a final set of 12 genes were selected to construct the multivariate Cox prognostic model. Among the 12 selected genes, 5 genes, STAU1, ADGRF1, ATF7IP2, MALL and KRT23, were adverse prognostic factors for patients, while seven genes, NDUFB1, CNPY2, ZNF394, PIN4, FZD8, NBPF26 and EPYC, were positive prognostic factors. An equation for risk score was thus constructed from the final multivariate Cox model. The model performance was tested in the sequestered TCGA testing dataset and validated in external tissue microarray datasets (GSE4573, GSE31210 and GSE50081), demonstrating its efficacy in stratifying patients into high- and low-risk groups with significant survival difference both in the whole set (including stage IA and IB) and in the stage IA only subgroup of each set. The prognostic power remains significant after adjusting for standard clinical factors. When benchmarked against other prominent gene-signature based prognostic models, the model outperformed the rest in the TCGA testing dataset and in predicting long-term risk at eight years in all three validation datasets. CONCLUSION The 12-gene prognostic model may serve as a useful complementary clinical risk-stratification tool for stage I and especially stage IA lung squamous cell carcinoma patients to guide clinical decision making.
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Affiliation(s)
- K Wang
- School of Clinical Medicine, The University of Cambridge, Cambridge, UK.,School of Medicine, The University of Leeds, Leeds, UK
| | - Y Li
- School of Medicine, The University of Manchester, Manchester, UK
| | - J Wang
- School of Public Health, Medical College of Soochow University, 199 Renai Rd., Suzhou, 215123, Jiangsu, China
| | - R Chen
- Respiratory Department, The Second Affiliated Hospital of the Soochow University, Suzhou, 215004, China.
| | - J Li
- School of Public Health, Medical College of Soochow University, 199 Renai Rd., Suzhou, 215123, Jiangsu, China.
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