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Rostom MM, Rashwan AA, Sotiropoulou CD, Hozayen SZ, Abdelhamid AM, Abdelhalim MM, Eltahtawy O, Emara HM, Elemam NM, Kontos CK, Youness RA. MIAT: A pivotal oncogenic long noncoding RNA tunning the hallmarks of solid malignancies. Transl Oncol 2025; 54:102329. [PMID: 40014977 PMCID: PMC11910686 DOI: 10.1016/j.tranon.2025.102329] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2024] [Revised: 01/06/2025] [Accepted: 02/13/2025] [Indexed: 03/01/2025] Open
Abstract
Long non-coding RNAs (LncRNAs) have emerged as intriguing players in cellular regulation, challenging the traditional view of non-coding RNAs as mere "dark genome". Non-coding DNA makes up most of the human genome and plays a pivotal role in cancer development. These RNA molecules, which do not code for proteins, have captivated researchers with their diverse and crucial roles in gene regulation, chromatin dynamics, and other cellular processes. In several physiological and pathological circumstances, lncRNAs serve critical functions. This review will tackle the complex function of the lncRNA myocardial infarction-associated transcript (MIAT) in various solid malignancies. A special emphasis would be directed on the correlation between cancer patients' clinicopathological features and the expression profile of MIAT. MIAT is a oncogenic regulator in many malignant tumors, where it can control the growth, invasion, metastasis, and resistance to death of cells. As a result, MIAT is thought to be a possible biomarker and therapeutic target for cancer patients. The biological functions, mechanisms and potential clinical implications of MIAT during carcinogenesis and finally the current possible therapeutic approaches targeting MIAT are also outlined in this review.
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Affiliation(s)
- Monica M Rostom
- Pharmacology and Toxicology Department, Faculty of Pharmacy and Biotechnology, German University in Cairo, 11835, Cairo, Egypt
| | - Alaa A Rashwan
- Biotechnology Graduate Program, School of Sciences and Engineering, The American University in Cairo (AUC), 11835, Cairo, Egypt
| | - Christina D Sotiropoulou
- Department of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, 15701, Athens, Greece
| | - Sama Z Hozayen
- Molecular Biology and Biochemistry Department, Molecular Genetics Research Team (MGRT), Faculty of Biotechnology, German International University (GIU), 11835, Cairo, Egypt
| | | | - Miriam Mokhtar Abdelhalim
- Molecular Biology and Biochemistry Department, Molecular Genetics Research Team (MGRT), Faculty of Biotechnology, German International University (GIU), 11835, Cairo, Egypt
| | - Omar Eltahtawy
- Molecular Biology and Biochemistry Department, Molecular Genetics Research Team (MGRT), Faculty of Biotechnology, German International University (GIU), 11835, Cairo, Egypt
| | - Hadir M Emara
- Molecular Biology and Biochemistry Department, Molecular Genetics Research Team (MGRT), Faculty of Biotechnology, German International University (GIU), 11835, Cairo, Egypt; Department of Nanotechnology, School of Sciences and Engineering, The American University in Cairo (AUC), 11835, Cairo, Egypt
| | - Noha M Elemam
- Clinical Sciences Department, College of Medicine, University of Sharjah, 27272, Sharjah, UAE; Research Institute for Medical and Health Sciences, University of Sharjah, 27272, Sharjah, UAE
| | - Christos K Kontos
- Department of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, 15701, Athens, Greece
| | - Rana A Youness
- Molecular Biology and Biochemistry Department, Molecular Genetics Research Team (MGRT), Faculty of Biotechnology, German International University (GIU), 11835, Cairo, Egypt.
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Wei X, Si A, Zhao S, Fu Y, Li J, Aishanjiang K, Ma Y, Yu C, Yu B, Cui C, Wang H, Kong X, Li S, Kong X, Tong Y, Wu H. CircUCK2(2,3) promotes cancer progression and enhances synergistic cytotoxicity of lenvatinib with EGFR inhibitors via activating CNIH4-TGFα-EGFR signaling. Cell Mol Biol Lett 2025; 30:15. [PMID: 39885395 PMCID: PMC11781035 DOI: 10.1186/s11658-025-00690-1] [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: 08/20/2024] [Accepted: 01/08/2025] [Indexed: 02/01/2025] Open
Abstract
BACKGROUND Circular (circ)RNAs have emerged as crucial contributors to cancer progression. Nonetheless, the expression regulation, biological functions, and underlying mechanisms of circRNAs in mediating hepatocellular carcinoma (HCC) progression remain insufficiently elucidated. METHODS We identified circUCK2(2,3) through circRNA sequencing, RT-PCR, and Sanger sequencing. CircUCK2(2,3) levels were measured in two independent HCC cohorts using quantitative real-time PCR (qRT-PCR). We explored the functions of circUCK2(2,3) using gain- and loss-of-function assays. Techniques such as RNA-sequencing, RNA immunoprecipitation (RIP), polysome fractionation, RNA pulldown, dual luciferase reporter assay, inhibitors of EGFR downstream signaling, CRISPR-Cas9, and medium transfer assays were employed to investigate the regulatory mechanisms and the protumoral activities of circUCK2(2,3). Additionally, in vitro cytotoxic assays and patient-derived xenograft (PDX) models assessed the effects of circUCK2(2,3) on the cytotoxic synergy of lenvatinib and EGFR inhibitors. RESULTS CircUCK2(2,3) is upregulated in HCC tissues and serves as an independent risk factor for poor recurrence-free survival. The expression of circUCK2(2,3) is independent on its host gene, UCK2, but is regulated by its upstream promoter and flanking inverted complementary sequences. Functionally, circUCK2(2,3) enhances HCC proliferation, migration, and invasion, both in vitro and in vivo. Mechanistically, by sponging miR-149-5p, circUCK2(2,3) increases CNIH4 levels, which in turn amplifies TGFα secretion, resulting in the activation of EGFR and downstream pAKT and pERK signaling pathways. Moreover, circUCK2(2,3) overexpression sensitizes HCC cells to EGFR inhibitors, and increases the synergistic cytotoxicity of combined lenvatinib and EGFR inhibitor treatment. CONCLUSIONS CircUCK2(2,3) regulates a novel oncogenic pathway, miR-149-5p-CNIH4-TGFα-EGFR, in HCC, presenting a viable therapeutic target and biomarker for the precision treatment of HCC.
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Affiliation(s)
- Xindong Wei
- Clinical Research Center, Jiading District Central Hospital Affiliated to Shanghai University of Medicine and Health Sciences, Shanghai, 201800, China
- Central Laboratory, ShuGuang Hospital Affiliated to Shanghai University of Chinese Traditional Medicine, Shanghai, 201203, China
- Collaborative Research Center for Biomedicines, Shanghai University of Medicine and Health Sciences, Shanghai, 201318, China
| | - Anfeng Si
- Department of General Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210015, China
| | - Shuai Zhao
- Department of Transplantation, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China
| | - Yi Fu
- Clinical Research Center, Jiading District Central Hospital Affiliated to Shanghai University of Medicine and Health Sciences, Shanghai, 201800, China
- Collaborative Research Center for Biomedicines, Shanghai University of Medicine and Health Sciences, Shanghai, 201318, China
| | - Jilei Li
- Clinical Research Center, Jiading District Central Hospital Affiliated to Shanghai University of Medicine and Health Sciences, Shanghai, 201800, China
- Collaborative Research Center for Biomedicines, Shanghai University of Medicine and Health Sciences, Shanghai, 201318, China
| | - Kedeerya Aishanjiang
- Clinical Research Center, Jiading District Central Hospital Affiliated to Shanghai University of Medicine and Health Sciences, Shanghai, 201800, China
- Department of Transplantation, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China
- People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, 831399, China
| | - Yujie Ma
- Clinical Research Center, Jiading District Central Hospital Affiliated to Shanghai University of Medicine and Health Sciences, Shanghai, 201800, China
- Collaborative Research Center for Biomedicines, Shanghai University of Medicine and Health Sciences, Shanghai, 201318, China
| | - Chang Yu
- Central Laboratory, ShuGuang Hospital Affiliated to Shanghai University of Chinese Traditional Medicine, Shanghai, 201203, China
| | - Bo Yu
- School of Clinical Medicine, Shanghai University of Medicine and Health Sciences, Shanghai, 201318, China
| | - Chunhong Cui
- Basic Medical College, Shanghai University of Medicine and Health Sciences, Shanghai, 201318, China
| | - Hui Wang
- Basic Medical College, Shanghai University of Medicine and Health Sciences, Shanghai, 201318, China
| | - Xianming Kong
- Collaborative Research Center for Biomedicines, Shanghai University of Medicine and Health Sciences, Shanghai, 201318, China
| | - Shibo Li
- Department of Infectious Disease, Zhoushan Hospital, Wenzhou Medical University, Zhoushan, 316100, China.
| | - Xiaoni Kong
- Central Laboratory, ShuGuang Hospital Affiliated to Shanghai University of Chinese Traditional Medicine, Shanghai, 201203, China.
| | - Ying Tong
- Department of Liver Surgery, School of Medicine, Renji Hospital, Shanghai JiaoTong University, Shanghai, 200003, China.
| | - Hailong Wu
- Clinical Research Center, Jiading District Central Hospital Affiliated to Shanghai University of Medicine and Health Sciences, Shanghai, 201800, China.
- Collaborative Research Center for Biomedicines, Shanghai University of Medicine and Health Sciences, Shanghai, 201318, China.
- School of Pharmacy, Joint Innovation Laboratory for Cell Therapy Technology, Shanghai University of Medicine and Health Sciences, Shanghai, 201318, China.
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Zhang M, Guo R, Yuan Z, Wang H. Lipid Nanoparticle (LNP) -A Vector Suitable for Evolving Therapies for Advanced Hepatocellular Carcinoma (HCC). GLOBAL CHALLENGES (HOBOKEN, NJ) 2025; 9:2400217. [PMID: 39802046 PMCID: PMC11717671 DOI: 10.1002/gch2.202400217] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/17/2024] [Revised: 11/07/2024] [Indexed: 01/16/2025]
Abstract
Hepatocellular carcinoma (HCC) stands as the predominant form of primary liver cancer, characterized by a dismal prognosis. Therapeutic options for advanced HCC remain sparse, with efficacy significantly hampered by the emergence of drug resistance. In parallel with research into novel pharmacological agents, advances in drug delivery systems represent a promising avenue for overcoming resistance. Lipid nanoparticles (LNPs) have demonstrated considerable efficacy in the delivery of nucleic acid-based therapeutics and hold potential for broader applications in drug delivery. This review describes the development of LNPs tailored for HCC treatment and consolidates recent investigations using LNPs to target HCC.
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Affiliation(s)
- Mingxuan Zhang
- Department of Radiation OncologyCancer Center of Peking University Third HospitalPeking University Third HospitalHaidian, 49 Huayuan North RoadBeijing100191China
| | - Ruiping Guo
- Department of Radiation OncologyCancer Center of Peking University Third HospitalPeking University Third HospitalHaidian, 49 Huayuan North RoadBeijing100191China
| | - Zhuhui Yuan
- Department of Radiation OncologyCancer Center of Peking University Third HospitalPeking University Third HospitalHaidian, 49 Huayuan North RoadBeijing100191China
| | - Hao Wang
- Department of Radiation OncologyCancer Center of Peking University Third HospitalPeking University Third HospitalHaidian, 49 Huayuan North RoadBeijing100191China
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Yu Y, Lu XH, Mu JS, Meng JY, Sun JS, Chen HX, Yan Y, Meng K. N6-methyladenosine-modified long non-coding RNA KIF9-AS1 promotes stemness and sorafenib resistance in hepatocellular carcinoma by upregulating SHOX2 expression. World J Gastroenterol 2024; 30:5174-5190. [PMID: 39735272 PMCID: PMC11612700 DOI: 10.3748/wjg.v30.i48.5174] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Revised: 09/26/2024] [Accepted: 11/08/2024] [Indexed: 11/29/2024] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is a prevalent and aggressive tumor. Sorafenib is the first-line treatment for patients with advanced HCC, but resistance to sorafenib has become a significant challenge in this therapy. Cancer stem cells play a crucial role in sorafenib resistance in HCC. Our previous study revealed that the long non-coding RNA (lncRNA) KIF9-AS1 is an oncogenic gene in HCC. However, the role of KIF9-AS1 in drug resistance and cancer stemness in HCC remains unclear. Herein, we aimed to investigate the function and mechanism of the lncRNA KIF9-AS1 in cancer stemness and drug resistance in HCC. AIM To describe the role of the lncRNA KIF9-AS1 in cancer stemness and drug resistance in HCC and elucidate the underlying mechanism. METHODS Tumor tissue and adjacent non-cancerous tissue samples were collected from HCC patients. Sphere formation was quantified via a tumor sphere assay. Cell viability, proliferation, and apoptosis were evaluated via Cell Counting Kit-8, flow cytometry, and colony formation assays, respectively. The interactions between the lncRNA KIF9-AS1 and its downstream targets were confirmed via RNA immunoprecipitation and coimmunoprecipitation. The tumorigenic role of KIF9-AS1 was validated in a mouse model. RESULTS Compared with that in normal controls, the expression of the lncRNA KIF9-AS1 was upregulated in HCC tissues. Knockdown of KIF9-AS1 inhibited stemness and attenuated sorafenib resistance in HCC cells. Mechanistically, N6-methyladenosine modification mediated by methyltransferase-like 3/insulin-like growth factor 2 mRNA-binding protein 1 stabilized and increased the expression of KIF9-AS1. Additionally, KIF9-AS1 increased the stability and expression of short stature homeobox 2 by promoting ubiquitin-specific peptidase 1-induced deubiquitination. Furthermore, depletion of KIF9-AS1 alleviated sorafenib resistance in a xenograft mouse model of HCC. CONCLUSION The N6-methyladenosine-modified lncRNA KIF9-AS1 promoted stemness and sorafenib resistance in HCC by upregulating short stature homeobox 2 expression.
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MESH Headings
- Carcinoma, Hepatocellular/drug therapy
- Carcinoma, Hepatocellular/genetics
- Carcinoma, Hepatocellular/pathology
- Carcinoma, Hepatocellular/metabolism
- Sorafenib/pharmacology
- Sorafenib/therapeutic use
- Humans
- Liver Neoplasms/genetics
- Liver Neoplasms/drug therapy
- Liver Neoplasms/pathology
- Liver Neoplasms/metabolism
- Drug Resistance, Neoplasm/genetics
- RNA, Long Noncoding/genetics
- RNA, Long Noncoding/metabolism
- Animals
- Neoplastic Stem Cells/drug effects
- Neoplastic Stem Cells/metabolism
- Neoplastic Stem Cells/pathology
- Mice
- Gene Expression Regulation, Neoplastic
- Up-Regulation
- Adenosine/analogs & derivatives
- Adenosine/metabolism
- Adenosine/pharmacology
- Cell Line, Tumor
- Male
- Cell Proliferation/drug effects
- Homeodomain Proteins/genetics
- Homeodomain Proteins/metabolism
- Xenograft Model Antitumor Assays
- Apoptosis/drug effects
- Mice, Nude
- Antineoplastic Agents/pharmacology
- Antineoplastic Agents/therapeutic use
- Methyltransferases/metabolism
- Methyltransferases/genetics
- Female
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Affiliation(s)
- Yong Yu
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese People’s Liberation Army General Hospital, Beijing 100853, China
| | - Xiang-Hong Lu
- Department of Intensive Care Medicine, The First Medical Center, Chinese People’s Liberation Army General Hospital, Beijing 100853, China
| | - Jin-Song Mu
- Department of Intensive Care Medicine, The Fifth Medical Center, Chinese People’s Liberation Army General Hospital, Beijing 100039, China
| | - Jiang-Yun Meng
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese People’s Liberation Army General Hospital, Beijing 100853, China
| | - Jiang-Shan Sun
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese People’s Liberation Army General Hospital, Beijing 100853, China
| | - Hai-Xu Chen
- Institute of Geriatrics and National Clinical Research Center of Geriatrics Disease, The Second Medical Center, Chinese People’s Liberation Army General Hospital, Beijing 100853, China
| | - Yang Yan
- Department of General Surgery, The First Medical Center, Chinese People’s Liberation Army General Hospital, Beijing 100853, China
| | - Ke Meng
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese People’s Liberation Army General Hospital, Beijing 100853, China
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Tian Y, Zhang M, Liu LX, Wang ZC, Liu B, Huang Y, Wang X, Ling YZ, Wang F, Feng X, Tu Y. Exploring non-coding RNA mechanisms in hepatocellular carcinoma: implications for therapy and prognosis. Front Immunol 2024; 15:1400744. [PMID: 38799446 PMCID: PMC11116607 DOI: 10.3389/fimmu.2024.1400744] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2024] [Accepted: 04/03/2024] [Indexed: 05/29/2024] Open
Abstract
Hepatocellular carcinoma (HCC) is a significant contributor to cancer-related deaths in the world. The development and progression of HCC are closely correlated with the abnormal regulation of non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). Important biological pathways in cancer biology, such as cell proliferation, death, and metastasis, are impacted by these ncRNAs, which modulate gene expression. The abnormal expression of non-coding RNAs in HCC raises the possibility that they could be applied as new biomarkers for diagnosis, prognosis, and treatment targets. Furthermore, by controlling the expression of cancer-related genes, miRNAs can function as either tumor suppressors or oncogenes. On the other hand, lncRNAs play a role in the advancement of cancer by interacting with other molecules within the cell, which, in turn, affects processes such as chromatin remodeling, transcription, and post-transcriptional processes. The importance of ncRNA-driven regulatory systems in HCC is being highlighted by current research, which sheds light on tumor behavior and therapy response. This research highlights the great potential of ncRNAs to improve patient outcomes in this difficult disease landscape by augmenting the present methods of HCC care through the use of precision medicine approaches.
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Affiliation(s)
- Yu Tian
- Research Center, The Huizhou Central People’s Hospital, Guangdong Medical University, Huizhou, Guangdong, China
- School of Public Health, Benedictine University, Lisle, IL, United States
| | - Meng Zhang
- Department of Hepatobiliary Surgery, Affiliated Hospital of Hebei University, Baoding, China
| | - Li-xia Liu
- Department of Ultrasound, Hebei Key Laboratory of Precise Imaging of Inflammation Related Tumors, Affiliated Hospital of Hebei University, Baoding, Hebei, China
| | - Zi-chao Wang
- Department of Ultrasound, Hebei Key Laboratory of Precise Imaging of Inflammation Related Tumors, Affiliated Hospital of Hebei University, Baoding, Hebei, China
| | - Bin Liu
- Central Laboratory, Hebei Key Laboratory of Cancer Radiotherapy and Chemotherapy, Affiliated Hospital of Hebei University, Baoding, Hebei, China
| | - Youcai Huang
- Research Center, The Huizhou Central People’s Hospital, Guangdong Medical University, Huizhou, Guangdong, China
| | - Xiaoling Wang
- Research Center, The Huizhou Central People’s Hospital, Guangdong Medical University, Huizhou, Guangdong, China
| | - Yun-zhi Ling
- Research Center, The Huizhou Central People’s Hospital, Guangdong Medical University, Huizhou, Guangdong, China
| | - Furong Wang
- Department of Pathology, The Huizhou Central People’s Hospital, Guangdong Medical University, Huizhou, Guangdong, China
| | - Xiaoqiang Feng
- Center of Stem Cell and Regenerative Medicine, Gaozhou People’s Hospital, Gaozhou, Guangdong, China
| | - Yanyang Tu
- Research Center, The Huizhou Central People’s Hospital, Guangdong Medical University, Huizhou, Guangdong, China
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Zhang J, Wu L, Wang C, Xie X, Han Y. Research Progress of Long Non-Coding RNA in Tumor Drug Resistance: A New Paradigm. Drug Des Devel Ther 2024; 18:1385-1398. [PMID: 38689609 PMCID: PMC11060174 DOI: 10.2147/dddt.s448707] [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: 11/23/2023] [Accepted: 03/25/2024] [Indexed: 05/02/2024] Open
Abstract
In the past few decades, chemotherapy has been one of the most effective cancer treatment options. Drug resistance is currently one of the greatest obstacles to effective cancer treatment. Even though drug resistance mechanisms have been extensively investigated, they have not been fully elucidated. Recent genome-wide investigations have revealed the existence of a substantial quantity of long non-coding RNAs (lncRNAs) transcribed from the human genome, which actively participate in numerous biological processes, such as transcription, splicing, epigenetics, the cell cycle, cell differentiation, development, pluripotency, immune microenvironment. The abnormal expression of lncRNA is considered a contributing factor to the drug resistance. Furthermore, drug resistance may be influenced by genetic and epigenetic variations, as well as individual differences in patient treatment response, attributable to polymorphisms in metabolic enzyme genes. This review focuses on the mechanism of lncRNAs resistance to target drugs in the study of tumors with high mortality, aiming to establish a theoretical foundation for targeted therapy.
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Affiliation(s)
- Jing Zhang
- Laboratory of Tissue Engineering, Faculty of Life Science, Northwest University, Xi’an, Shaanxi, People’s Republic of China
| | - Le Wu
- Laboratory of Tissue Engineering, Faculty of Life Science, Northwest University, Xi’an, Shaanxi, People’s Republic of China
| | - Chenchen Wang
- Department of Critical Care Medicine, the 940th Hospital of Joint Logistics Support Force of PLA, Lanzhou, Gansu, People’s Republic of China
| | - Xin Xie
- Laboratory of Tissue Engineering, Faculty of Life Science, Northwest University, Xi’an, Shaanxi, People’s Republic of China
| | - Yuying Han
- Laboratory of Tissue Engineering, Faculty of Life Science, Northwest University, Xi’an, Shaanxi, People’s Republic of China
- Department of Critical Care Medicine, the 940th Hospital of Joint Logistics Support Force of PLA, Lanzhou, Gansu, People’s Republic of China
- Science and Education Department, Xi’an No. 5 Hospital, Xi’an, Shaanxi, People’s Republic of China
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Saleh RO, Alkhafaji AT, Mohammed JS, Bansal P, Kaur H, Ahmad I, Hjazi A, Mohammed IH, Jawad MA, Zwamel AH. LncRNA NEAT1 in the pathogenesis of liver-related diseases. Cell Biochem Funct 2024; 42:e4006. [PMID: 38622913 DOI: 10.1002/cbf.4006] [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: 02/24/2024] [Revised: 03/20/2024] [Accepted: 03/27/2024] [Indexed: 04/17/2024]
Abstract
Nuclear paraspeckle assembly transcript 1 (NEAT1) is a long noncoding RNA (lncRNA) that is widely expressed in a variety of mammalian cell types. Altered expression levels of the lncRNA NEAT1 have been reported in liver-related disorders including cancer, fatty liver disease, liver fibrosis, viral hepatitis, and hepatic ischemia. lncRNA NEAT1 mostly acts as a competing endogenous RNA (ceRNA) to sponge various miRNAs (miRs) to regulate different functions. In regard to hepatic cancers, the elevated expression of NEAT1 has been reported to have a relation with the proliferation, migration, angiogenesis, apoptosis, as well as epithelial-mesenchymal transition (EMT) of cancer cells. Furthermore, NEAT1 upregulation has contributed to the pathogenesis of other liver diseases such as fibrosis. In this review, we summarize and discuss the molecular mechanisms by which NEAT1 contributes to liver-related disorders including acute liver failure, nonalcoholic fatty liver disease (NAFLD), liver fibrosis, and liver carcinoma, providing novel insights and introducing NEAT1 as a potential therapeutic target in these diseases.
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Affiliation(s)
- Raed Obaid Saleh
- Department of Medical Laboratory Techniques, Al-Maarif University College, Al-Anbar, Iraq
| | | | | | - Pooja Bansal
- Department of Biotechnology and Genetics, Jain (Deemed-to-be) University, Bengaluru, Karnataka, India
- Department of Allied Healthcare and Sciences, Vivekananda Global University, Jaipur, Rajasthan, India
| | - Harpreet Kaur
- School of Basic & Applied Sciences, Shobhit University, Gangoh, Uttar Pradesh, India
- Department of Health & Allied Sciences, Arka Jain University, Jamshedpur, Jharkhand, India
| | - Irfan Ahmad
- Department of Clinical Laboratory Sciences, College of Applied Medical Science, King Khalid University, Abha, Saudi Arabia
| | - Ahmed Hjazi
- Department of Medical Laboratory, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Al-Kharj, Saudi Arabia
| | | | - Mohammed Abed Jawad
- Department of Medical Laboratories Technology, Al-Nisour University College, Baghdad, Iraq
| | - Ahmed Hussein Zwamel
- Medical laboratory technique college, the Islamic University, Najaf, Iraq
- Medical laboratory technique college, the Islamic University of Al Diwaniyah, Al Diwaniyah, Iraq
- Medical laboratory technique college, the Islamic University of Babylon, Babylon, Iraq
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8
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Tang Z, Li X, Zheng Y, Liu J, Liu C, Li X. The role of competing endogenous RNA network in the development of hepatocellular carcinoma: potential therapeutic targets. Front Cell Dev Biol 2024; 12:1341999. [PMID: 38357004 PMCID: PMC10864455 DOI: 10.3389/fcell.2024.1341999] [Citation(s) in RCA: 12] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Accepted: 01/16/2024] [Indexed: 02/16/2024] Open
Abstract
The current situation of hepatocellular carcinoma (HCC) management is challenging due to its high incidence, mortality, recurrence and metastasis. Recent advances in gene genetic and expression regulation have unveiled the significant role of non-coding RNA (ncRNA) in various cancers. This led to the formulation of the competing endogenous RNA (ceRNA) hypothesis, which posits that both coding RNA and ncRNA, containing miRNA response elements (MRE), can share the same miRNA sequence. This results in a competitive network between ncRNAs, such as lncRNA and mRNA, allowing them to regulate each other. Extensive research has highlighted the crucial role of the ceRNA network in HCC development, impacting various cellular processes including proliferation, metastasis, cell death, angiogenesis, tumor microenvironment, organismal immunity, and chemotherapy resistance. Additionally, the ceRNA network, mediated by lncRNA or circRNA, offers potential in early diagnosis and prevention of HCC. Consequently, ceRNAs are emerging as therapeutic targets for HCC. The complexity of these gene networks aligns with the multi-target approach of traditional Chinese medicine (TCM), presenting a novel perspective for TCM in combating HCC. Research is beginning to show that TCM compounds and prescriptions can affect HCC progression through the ceRNA network, inhibiting proliferation and metastasis, and inducing apoptosis. Currently, the lncRNAs TUG1, NEAT1, and CCAT1, along with their associated ceRNA networks, are among the most promising ncRNAs for HCC research. However, this field is still in its infancy, necessitating advanced technology and extensive basic research to fully understand the ceRNA network mechanisms of TCM in HCC treatment.
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Affiliation(s)
- Ziwei Tang
- The Ninth People’s Hospital of Chongqing, Chongqing, China
| | - Xue Li
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yanfeng Zheng
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China
- Chongqing Medical and Pharmaceutical College, Chongqing, China
| | - Jin Liu
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Chao Liu
- Chongqing Chemical Industry Vocational College, Chongqing, China
| | - Xia Li
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China
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9
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Shen M, Zhang Q, Pan W, Wang B. CircUCK2 promotes hepatocellular carcinoma development by upregulating UCK2 in a mir-149-5p-dependent manner. Discov Oncol 2024; 15:14. [PMID: 38245591 PMCID: PMC10799813 DOI: 10.1007/s12672-024-00863-y] [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] [Received: 08/09/2023] [Accepted: 01/08/2024] [Indexed: 01/22/2024] Open
Abstract
BACKGROUND Circular RNAs (circRNAs) participate in the regulation of Hepatocellular Carcinoma (HCC) progression. The objective of this study was to explore the function and mechanism of circUCK2 in HCC development. METHODS The RNA levels of circUCK2, miR-149-5p and uridine-cytidine kinase 2 (UCK2) were examined by quantitative real-time polymerase chain reaction (qRT-PCR). EdU incorporation assay and colony formation assay were respectively performed to analyze cell proliferation and colony formation. Wound healing assay and transwell assay were conducted for cell migration and invasion. Flow cytometry was used for cell apoptosis analysis. Western blot assay was conducted to determine the protein levels of E-cadherin, N-cadherin, matrix metallopeptidase 9 (MMP-9) and UCK2. Dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay and RNA pull-down assay were conducted to confirm the interaction between miR-149-5p and circUCK2 or UCK2. The xenograft model was established to explore the role of circUCK2 in tumor growth in vivo. RESULTS CircUCK2 level was elevated in HCC, and circUCK2 depletion suppressed HCC cell proliferation, colony formation, migration and invasion and accelerated cell apoptosis. Mechanistically, circUCK2 could positively modulate UCK2 expression by interacting with miR-149-5p. Furthermore, the repressive effects of circUCK2 knockdown on the malignant behaviors of HCC cells were alleviated by UCK2 overexpression or miR-149-5p inhibition. The promoting effects of circUCK2 overexpression on HCC cell malignancy were alleviated by UCK2 silencing or miR-149-5p introduction. Additionally, circUCK2 knockdown hampered tumor growth in vivo. CONCLUSION CircUCK2 contributed to HCC malignant progression in vitro and in vivo via targeting miR-149-5p/UCK2 axis, demonstrating that circUCK2 might be a novel therapeutic target for HCC.
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Affiliation(s)
- Minghai Shen
- Department of General Surgury, Xixi Hospital of Hangzhou, Hangzhou, 310023, China
| | - Qinghua Zhang
- Department of General Surgury, Xixi Hospital of Hangzhou, Hangzhou, 310023, China
| | - Wanneng Pan
- Department of General Surgury, Xixi Hospital of Hangzhou, Hangzhou, 310023, China
| | - Bei Wang
- Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, No. 79, Qingchun Road, Shangcheng District, Hangzhou, 310023, China.
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10
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Jing F, Li X, Jiang H, Sun J, Guo Q. Combating drug resistance in hepatocellular carcinoma: No awareness today, no action tomorrow. Biomed Pharmacother 2023; 167:115561. [PMID: 37757493 DOI: 10.1016/j.biopha.2023.115561] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Revised: 09/18/2023] [Accepted: 09/19/2023] [Indexed: 09/29/2023] Open
Abstract
Hepatocellular carcinoma (HCC), the sixth most common cancer worldwide, is associated with a high degree of malignancy and poor prognosis. Patients with early HCC may benefit from surgical resection to remove tumor tissue and a margin of healthy tissue surrounding it. Unfortunately, most patients with HCC are diagnosed at an advanced or distant stage, at which point resection is not feasible. Systemic therapy is now routinely prescribed to patients with advanced HCC; however, drug resistance has become a major obstacle to the treatment of HCC and exploring purported mechanisms promoting drug resistance remains a challenge. Here, we focus on the determinants of drug resistance from the perspective of non-coding RNAs (ncRNAs), liver cancer stem cells (LCSCs), autophagy, epithelial-mesenchymal transition (EMT), exosomes, ferroptosis, and the tumor microenvironment (TME), with the aim to provide new insights into HCC treatment.
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Affiliation(s)
- Fanbo Jing
- The department of clinical pharmacy. The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Xiao Li
- The department of clinical pharmacy. The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Hui Jiang
- Qingdao Haici Hospital, Qingdao 266000, China
| | - Jialin Sun
- The department of clinical pharmacy. The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Qie Guo
- The department of clinical pharmacy. The Affiliated Hospital of Qingdao University, Qingdao, China.
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11
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Romeo M, Dallio M, Scognamiglio F, Ventriglia L, Cipullo M, Coppola A, Tammaro C, Scafuro G, Iodice P, Federico A. Role of Non-Coding RNAs in Hepatocellular Carcinoma Progression: From Classic to Novel Clinicopathogenetic Implications. Cancers (Basel) 2023; 15:5178. [PMID: 37958352 PMCID: PMC10647270 DOI: 10.3390/cancers15215178] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2023] [Accepted: 10/25/2023] [Indexed: 11/15/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a predominant malignancy with increasing incidences and mortalities worldwide. In Western countries, the progressive affirmation of Non-alcoholic Fatty Liver Disease (NAFLD) as the main chronic liver disorder in which HCC occurrence is appreciable even in non-cirrhotic stages, constitutes a real health emergency. In light of this, a further comprehension of molecular pathways supporting HCC onset and progression represents a current research challenge to achieve more tailored prognostic models and appropriate therapeutic approaches. RNA non-coding transcripts (ncRNAs) are involved in the regulation of several cancer-related processes, including HCC. When dysregulated, these molecules, conventionally classified as "small ncRNAs" (sncRNAs) and "long ncRNAs" (lncRNAs) have been reported to markedly influence HCC-related progression mechanisms. In this review, we describe the main dysregulated ncRNAs and the relative molecular pathways involved in HCC progression, analyzing their implications in certain etiologically related contexts, and their applicability in clinical practice as novel diagnostic, prognostic, and therapeutic tools. Finally, given the growing evidence supporting the immune system response, the oxidative stress-regulated mechanisms, and the gut microbiota composition as relevant emerging elements mutually influencing liver-cancerogenesis processes, we investigate the relationship of ncRNAs with this triad, shedding light on novel pathogenetic frontiers of HCC progression.
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Affiliation(s)
- Mario Romeo
- Hepatogastroenterology Division, Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, Piazza Miraglia 2, 80138 Naples, Italy; (M.R.); (F.S.); (L.V.); (M.C.); (A.C.); (A.F.)
| | - Marcello Dallio
- Hepatogastroenterology Division, Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, Piazza Miraglia 2, 80138 Naples, Italy; (M.R.); (F.S.); (L.V.); (M.C.); (A.C.); (A.F.)
| | - Flavia Scognamiglio
- Hepatogastroenterology Division, Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, Piazza Miraglia 2, 80138 Naples, Italy; (M.R.); (F.S.); (L.V.); (M.C.); (A.C.); (A.F.)
| | - Lorenzo Ventriglia
- Hepatogastroenterology Division, Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, Piazza Miraglia 2, 80138 Naples, Italy; (M.R.); (F.S.); (L.V.); (M.C.); (A.C.); (A.F.)
| | - Marina Cipullo
- Hepatogastroenterology Division, Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, Piazza Miraglia 2, 80138 Naples, Italy; (M.R.); (F.S.); (L.V.); (M.C.); (A.C.); (A.F.)
| | - Annachiara Coppola
- Hepatogastroenterology Division, Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, Piazza Miraglia 2, 80138 Naples, Italy; (M.R.); (F.S.); (L.V.); (M.C.); (A.C.); (A.F.)
| | - Chiara Tammaro
- Biochemistry Division, Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, Piazza Miraglia 2, 80138 Naples, Italy; (C.T.); (G.S.)
| | - Giuseppe Scafuro
- Biochemistry Division, Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, Piazza Miraglia 2, 80138 Naples, Italy; (C.T.); (G.S.)
| | - Patrizia Iodice
- Division of Medical Oncology, AORN Azienda dei Colli, Monaldi Hospital, Via Leonardo Bianchi, 80131 Naples, Italy
| | - Alessandro Federico
- Hepatogastroenterology Division, Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, Piazza Miraglia 2, 80138 Naples, Italy; (M.R.); (F.S.); (L.V.); (M.C.); (A.C.); (A.F.)
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12
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Hua X, Li J, Shang M, He W, Gao P, Min L, Peng X. Pathogenesis of psoriasis via miR-149-5p/AKT1axis by long noncoding RNA BLACAT1. Skin Res Technol 2023; 29:e13339. [PMID: 37204030 PMCID: PMC10170242 DOI: 10.1111/srt.13339] [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: 12/31/2022] [Accepted: 04/19/2023] [Indexed: 05/20/2023]
Abstract
BACKGROUND Psoriasis is a chronic, complicated, and recurrent inflammatory skin disease, whose precise molecular mechanisms need to be further explored. The lncRNA bladder cancer-associated transcript 1 (BLACAT1) is aberrantly expressed in many cancers and associated with cellular hyperproliferation and may play a role in the pathogenesis of psoriasis. Thus, this study aimed at identifying the primary mechanism associated with BLACAT1 in psoriasis pathogenesis. MATERIALS AND METHODS Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was performed to detect the expression of BLACAT1 in psoriasis tissues. Cell proliferation and apoptosis were assessed using cell counting kit-8 and apoptosis assays, respectively. In vivo experiments and histopathological examinations were performed to investigate the effects of BLACAT1 on psoriasis. Dual-luciferase Reporter and RNA immunoprecipitation assays were used to evaluate the relationship among BLACAT1 and miR-149-5p and AKT1. RESULTS BLACAT1 was upregulated in psoriasis tissues. Overexpression exacerbated the clinical manifestation of psoriasis and increased the epidermal thickness in imiquimod-induced mice. BLACAT1 could promote proliferation and inhibit apoptosis of keratinocytes. Further studies demonstrated that BLACAT1 positively regulated AKT1 expression, functioning as a competing endogenous RNA (ceRNA) by sponging miR-149-5p. CONCLUSIONS The combination of lncRNA BLACAT1 and miR-149-5p regulates AKT1 expression and promotes psoriasis formation thus may provide a new direction for psoriasis treatment.
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Affiliation(s)
- Xiang Hua
- Department of DermatologyNanfang Hospital of Southern Medical UniversityGuangzhouChina
| | - JiaZheng Li
- Department of DermatologyNanfang Hospital of Southern Medical UniversityGuangzhouChina
- Department of DermatologyGuangzhou Panyu central hospitalGuangzhouChina
| | - MingWei Shang
- Department of DermatologyNanfang Hospital of Southern Medical UniversityGuangzhouChina
| | - WanMei He
- Department of DermatologyNanfang Hospital of Southern Medical UniversityGuangzhouChina
| | - PengFei Gao
- Department of DermatologyNanfang Hospital of Southern Medical UniversityGuangzhouChina
| | - Li Min
- Department of DermatologyNanfang Hospital of Southern Medical UniversityGuangzhouChina
| | - XueBiao Peng
- Department of DermatologyNanfang Hospital of Southern Medical UniversityGuangzhouChina
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13
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Farzaneh M, Masoodi T, Ghaedrahmati F, Radoszkiewicz K, Anbiyaiee A, Sheykhi-Sabzehpoush M, Rad NK, Uddin S, Jooybari SPM, Khoshnam SE, Azizidoost S. An updated review of contribution of long noncoding RNA-NEAT1 to the progression of human cancers. Pathol Res Pract 2023; 245:154380. [PMID: 37043964 DOI: 10.1016/j.prp.2023.154380] [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: 01/15/2023] [Revised: 02/12/2023] [Accepted: 02/16/2023] [Indexed: 02/26/2023]
Abstract
Long non-coding RNAs (lncRNAs) present pivotal roles in cancer tumorigenesis and progression. Recently, nuclear paraspeckle assembly transcript 1 (NEAT1) as a lncRNA has been shown to mediate cell proliferation, migration, and EMT in tumor cells. NEAT1 by targeting several miRNAs/mRNA axes could regulate cancer cell behavior. Therefore, NEAT1 may function as a potent biomarker for the prediction and treatment of some human cancers. In this review, we summarized various NEAT1-related signaling pathways that are critical in cancer initiation and progression.
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Affiliation(s)
- Maryam Farzaneh
- Fertility, Infertility and Perinatology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Tariq Masoodi
- Laboratory of Molecular and Metabolic Imaging, Cancer Research Department, Sidra Medicine, Doha 26999, Qatar
| | - Farhoodeh Ghaedrahmati
- Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Klaudia Radoszkiewicz
- Translational Platform for Regenerative Medicine, Mossakowski Medical Research Institute, Polish Academy of Sciences, Poland
| | - Amir Anbiyaiee
- Department of Surgery, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | | | - Niloofar Khoshdel Rad
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
| | - Shahab Uddin
- Translational Research Institute and Dermatology Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar
| | - Seyedeh Pardis Motiee Jooybari
- Department of Biology, Faculty of Basic Sciences and Engineering, University of Gonbad Kavous, Gonbad Kavus, Golestan, Iran
| | - Seyed Esmaeil Khoshnam
- Cellular and Molecular Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; Persian Gulf Physiology Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
| | - Shirin Azizidoost
- Atherosclerosis Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
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14
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Huang PS, Wang LY, Wang YW, Tsai MM, Lin TK, Liao CJ, Yeh CT, Lin KH. Evaluation and Application of Drug Resistance by Biomarkers in the Clinical Treatment of Liver Cancer. Cells 2023; 12:869. [PMID: 36980210 PMCID: PMC10047572 DOI: 10.3390/cells12060869] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Revised: 02/13/2023] [Accepted: 03/06/2023] [Indexed: 03/14/2023] Open
Abstract
Liver cancer is one of the most lethal cancers in the world, mainly owing to the lack of effective means for early monitoring and treatment. Accordingly, there is considerable research interest in various clinically applicable methods for addressing these unmet needs. At present, the most commonly used biomarker for the early diagnosis of liver cancer is alpha-fetoprotein (AFP), but AFP is sensitive to interference from other factors and cannot really be used as the basis for determining liver cancer. Treatment options in addition to liver surgery (resection, transplantation) include radiation therapy, chemotherapy, and targeted therapy. However, even more expensive targeted drug therapies have a limited impact on the clinical outcome of liver cancer. One of the big reasons is the rapid emergence of drug resistance. Therefore, in addition to finding effective biomarkers for early diagnosis, an important focus of current discussions is on how to effectively adjust and select drug strategies and guidelines for the treatment of liver cancer patients. In this review, we bring this thought process to the drug resistance problem faced by different treatment strategies, approaching it from the perspective of gene expression and molecular biology and the possibility of finding effective solutions.
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Affiliation(s)
- Po-Shuan Huang
- Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan; (P.-S.H.); (C.-J.L.)
| | - Ling-Yu Wang
- Department of Biochemistry and Molecular Biology, Chang Gung University, Taoyuan 333, Taiwan;
- Division of Hematology-Oncology, Chang Gung Memorial Hospital at Linkou, Taoyuan 333, Taiwan
| | - Yi-Wen Wang
- School of Nursing, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan;
| | - Ming-Ming Tsai
- Department of Nursing, Division of Basic Medical Sciences, Chang Gung University of Science and Technology, Taoyuan 333, Taiwan;
- Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 333, Taiwan
- Department of General Surgery, New Taipei Municipal Tu Cheng Hospital, New Taipei 236, Taiwan
| | - Tzu-Kang Lin
- Neurosurgery, School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City 24205, Taiwan;
- Neurosurgery, Department of Surgery, Fu Jen Catholic University Hospital, New Taipei City 24352, Taiwan
| | - Chia-Jung Liao
- Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan; (P.-S.H.); (C.-J.L.)
| | - Chau-Ting Yeh
- Liver Research Center, Chang Gung Memorial Hospital, Linkou, Taoyuan 333, Taiwan;
| | - Kwang-Huei Lin
- Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan; (P.-S.H.); (C.-J.L.)
- Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 333, Taiwan
- Liver Research Center, Chang Gung Memorial Hospital, Linkou, Taoyuan 333, Taiwan;
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15
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Hashemi M, Mirzaei S, Zandieh MA, Rezaei S, Amirabbas Kakavand, Dehghanpour A, Esmaeili N, Ghahremanzade A, Saebfar H, Heidari H, Salimimoghadam S, Taheriazam A, Entezari M, Ahn KS. Long non-coding RNAs (lncRNAs) in hepatocellular carcinoma progression: Biological functions and new therapeutic targets. PROGRESS IN BIOPHYSICS AND MOLECULAR BIOLOGY 2023; 177:207-228. [PMID: 36584761 DOI: 10.1016/j.pbiomolbio.2022.12.004] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Revised: 11/29/2022] [Accepted: 12/22/2022] [Indexed: 12/28/2022]
Abstract
Liver is an important organ in body that performs vital functions such as detoxification. Liver is susceptible to development of cancers, and hepatocellular carcinoma (HCC) is among them. 75-85% of liver cancer cases are related to HCC. Therefore, much attention has been directed towards understanding factors mediating HCC progression. LncRNAs are epigenetic factors with more than 200 nucleotides in length located in both nucleus and cytoplasm and they are promising candidates in cancer therapy. Directing studies towards understanding function of lncRNAs in HCC is of importance. LncRNAs regulate cell cycle progression and growth of HCC cells, and they can also induce/inhibit apoptosis in tumor cells. LncRNAs affect invasion and metastasis in HCC mainly by epithelial-mesenchymal transition (EMT) mechanism. Revealing the association between lncRNAs and downstream signaling pathways in HCC is discussed in the current manuscript. Infectious diseases can affect lncRNA expression in mediating HCC development and then, altered expression level of lncRNA is associated with drug resistance and radio-resistance. Biomarker application of lncRNAs and their role in prognosis and diagnosis of HCC are also discussed to pave the way for treatment of HCC patients.
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Affiliation(s)
- Mehrdad Hashemi
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Sepideh Mirzaei
- Department of Biology, Faculty of Science, Islamic Azad University, Science and Research Branch, Tehran, Iran
| | - Mohammad Arad Zandieh
- Department of Food Hygiene and Quality Control, Division of Epidemiology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
| | - Sahar Rezaei
- Faculty of Veterinary Medicine, Islamic Azad University, Science and Research Branch, Tehran, Iran
| | - Amirabbas Kakavand
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Amir Dehghanpour
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Negin Esmaeili
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Azin Ghahremanzade
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Hamidreza Saebfar
- European University Association, League of European Research Universities, University of Milan, Italy
| | - Hajar Heidari
- Department of Biomedical Sciences, School of Public Health University at Albany State University of New York, Albany, NY, 12208, USA
| | - Shokooh Salimimoghadam
- Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran
| | - Afshin Taheriazam
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Department of Orthopedics, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
| | - Maliheh Entezari
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
| | - Kwang Seok Ahn
- College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.
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16
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Tumor-Suppressive and Oncogenic Roles of microRNA-149-5p in Human Cancers. Int J Mol Sci 2022; 23:ijms231810823. [PMID: 36142734 PMCID: PMC9501226 DOI: 10.3390/ijms231810823] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Revised: 09/07/2022] [Accepted: 09/14/2022] [Indexed: 12/24/2022] Open
Abstract
Malignant tumors are always a critical threat to human health, with complex pathogenesis, numerous causative factors, and poor prognosis. The features of cancers, such as gene mutations, epigenetic alterations, and the activation and inhibition of signaling pathways in the organism, play important roles in tumorigenesis and prognosis. MicroRNA (miRNA) enables the control of various molecular mechanisms and plays a variety of roles in human cancers, such as radiation sensitivity and tumor immunity, through the regulation of target genes. MiR-149-5p participates in the process and is closely related to lipogenesis, the migration of vascular endothelial cells, and the expression of stem-cell-related proteins. In recent years, its role in cancer has dramatically increased. In this review, we summarize the regular physiological roles of miRNAs, specifically miR-149-5p, in the organism and discuss the tumor-suppressive or oncogenic roles of miR-149-5p in different human cancers with respect to signaling pathways involved in regulation. Possible clinical applications of miR-149-5p in future targeted therapies and prognosis improvement in oncology are suggested.
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17
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Investigation of Anti-Liver Cancer Activity of the Herbal Drug FDY003 Using Network Pharmacology. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:5765233. [PMID: 36118098 PMCID: PMC9481369 DOI: 10.1155/2022/5765233] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Accepted: 08/10/2022] [Indexed: 11/18/2022]
Abstract
Globally, liver cancer (LC) is the sixth-most frequently occurring and the second-most fatal malignancy, responsible for 0.83 million deaths annually. Although the application of herbal drugs in cancer therapies has increased, their anti-LC activity and relevant mechanisms have not been fully studied from a systems perspective. To address these issues, we conducted a system-perspective network pharmacological investigation into the activity and mechanisms underlying the action of the herbal drug. FDY003 reduced the viability of human LC treatment. FDY003 reduced the viability of human LC cells and elevated their chemosensitivity. There were a total of 16 potential bioactive chemical components in FDY003 and they had 91 corresponding targets responsible for the pathological processes in LC. These FDY003 targets were functionally involved in regulating the survival, proliferation, apoptosis, and cell cycle of LC cells. Additionally, we found that FDY003 may target key signaling cascades connected to diverse LC pathological mechanisms, namely, PI3K-Akt, focal adhesion, IL-17, FoxO, MAPK, and TNF pathways. Overall, this study contributed to integrative mechanistic insights into the anti-LC potential of FDY003.
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18
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Zhou H, Wang Y, Liu Z, Zhang Z, Xiong L, Wen Y. Recent advances of NEAT1-miRNA interactions in cancer. Acta Biochim Biophys Sin (Shanghai) 2022; 54:153-162. [PMID: 35538025 PMCID: PMC9827865 DOI: 10.3724/abbs.2021022] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Accepted: 07/20/2021] [Indexed: 11/25/2022] Open
Abstract
With high incidence rate, cancer is the main cause of death in humans. Non-coding RNAs, as novel master regulators, especially long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), play important roles in the regulation of tumorigenesis. lncRNA NEAT1 has recently gained much attention, as it is dysregulated in a broad spectrum of cancers, where it acts as either an oncogene or a tumor suppressor gene. Accumulating evidence shows that NEAT1 is correlated with the process of carcinogenesis, including proliferation, invasion, survival, drug resistance, and metastasis. NEAT1 is considered to be a biomarker and a novel therapeutic target for the diagnosis and prognosis of different cancer types. The mechanisms by which NEAT1 plays a critical role in cancers are mainly via interactions with miRNAs. NEAT1-miRNA regulatory networks play significant roles in tumorigenesis, which has attracted much attention from researchers around the world. In this review, we summarize the interaction of NEAT1 with miRNAs in the regulation of protein-coding genes in cancer. A better understanding of the NEAT1-miRNA interactions in cancer will help develop new diagnostic biomarkers and therapeutic approaches.
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Affiliation(s)
- Hui Zhou
- />Department of General SurgerySecond Xiangya HospitalCentral South UniversityChangsha410011China
| | - Yongxiang Wang
- />Department of General SurgerySecond Xiangya HospitalCentral South UniversityChangsha410011China
| | - Zhongtao Liu
- />Department of General SurgerySecond Xiangya HospitalCentral South UniversityChangsha410011China
| | - Zijian Zhang
- />Department of General SurgerySecond Xiangya HospitalCentral South UniversityChangsha410011China
| | - Li Xiong
- />Department of General SurgerySecond Xiangya HospitalCentral South UniversityChangsha410011China
| | - Yu Wen
- />Department of General SurgerySecond Xiangya HospitalCentral South UniversityChangsha410011China
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19
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A Review on the Role of miR-149-5p in the Carcinogenesis. Int J Mol Sci 2021; 23:ijms23010415. [PMID: 35008841 PMCID: PMC8745060 DOI: 10.3390/ijms23010415] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Revised: 12/28/2021] [Accepted: 12/29/2021] [Indexed: 02/07/2023] Open
Abstract
miR-149 is an miRNA with essential roles in carcinogenesis. This miRNA is encoded by the MIR149 gene on 2q37.3. The miR-149 hairpin produces miR-149-5p and miR-149-3p, which are the “guide” and the sister “passenger” strands, respectively. Deep sequencing experiments have shown higher prevalence of miR-149-5p compared with miR-149-3p. Notably, both oncogenic and tumor suppressive roles have been reported for miR-149-5p. In this review, we summarize the impact of miR-149-5p in the tumorigenesis and elaborate mechanisms of its involvement in this process in a variety of neoplastic conditions based on three lines of evidence, i.e., in vitro, in vivo and clinical settings.
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Zhao J, Li Q, Feng B, Wei D, Han Y, Li M, Wang Y, Luo Y, Jiang Y. MicroRNA‑149 inhibits cancer cell malignant phenotype by regulating Akt1 in C4‑2 CRPC cell line. Oncol Rep 2021; 46:258. [PMID: 34698359 PMCID: PMC8561672 DOI: 10.3892/or.2021.8209] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Accepted: 08/31/2021] [Indexed: 01/06/2023] Open
Abstract
Prostate cancer (PCa) is an androgen‑dependent disease. Androgen receptor (AR) has a crucial role in the development and progression of PCa. Recently, several microRNAs (miRNAs/miRs) involved in AR regulation have been associated with castration‑resistant prostate cancer (CRPC), the terminal stage of PCa. Nevertheless, the precise mechanism remains unclear. The present study aimed to identify a novel miR‑149 regulatory network and potential therapeutic target for CRPC. It was found that ectopic expression of miR‑149 mimic could inhibit AR expression, repress epithelial‑mesenchymal transition, induce cell cycle arrest and apoptosis in CRPC cell line C4‑2, whereas the miR‑149 inhibitor exerted the opposite effects. Furthermore, it was also revealed that miR‑149 could reduce the functional activity of the PI3K/Akt1 signaling pathway by targeting Akt1 protein, the key regulatory factor of the PI3K/Akt1 signaling pathway. Knockdown of Akt1 by short hairpin RNA increased apoptosis, reduced proliferation, and restrained migration and invasion in CRPC cells, with the effect of AR inhibition. In conclusion, these results revealed that miR‑149 acts as a tumor suppressor in CRPC cell line C4‑2 and restrains its progression through the AR signaling pathway by targeting Akt1. The miR‑149/Akt1/AR regulatory pathway may represent a novel PCa therapeutic target.
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Affiliation(s)
- Jiahui Zhao
- Department of Urology, Beijing Anzhen Hospital, Capital Medical University, Chaoyang, Beijing 100029, P.R. China
| | - Qiankun Li
- Department of Urology, Beijing Anzhen Hospital, Capital Medical University, Chaoyang, Beijing 100029, P.R. China
| | - Bingfu Feng
- Department of Urology, Beijing Anzhen Hospital, Capital Medical University, Chaoyang, Beijing 100029, P.R. China
| | - Dechao Wei
- Department of Urology, Beijing Anzhen Hospital, Capital Medical University, Chaoyang, Beijing 100029, P.R. China
| | - Yili Han
- Department of Urology, Beijing Anzhen Hospital, Capital Medical University, Chaoyang, Beijing 100029, P.R. China
| | - Mingchuan Li
- Department of Urology, Beijing Anzhen Hospital, Capital Medical University, Chaoyang, Beijing 100029, P.R. China
| | - Yongxing Wang
- Department of Urology, Beijing Anzhen Hospital, Capital Medical University, Chaoyang, Beijing 100029, P.R. China
| | - Yong Luo
- Department of Urology, Beijing Anzhen Hospital, Capital Medical University, Chaoyang, Beijing 100029, P.R. China
| | - Yongguang Jiang
- Department of Urology, Beijing Anzhen Hospital, Capital Medical University, Chaoyang, Beijing 100029, P.R. China
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21
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Ren FJ, Yao Y, Cai XY, Cai YT, Su Q, Fang GY. MiR-149-5p: An Important miRNA Regulated by Competing Endogenous RNAs in Diverse Human Cancers. Front Oncol 2021; 11:743077. [PMID: 34722295 PMCID: PMC8554335 DOI: 10.3389/fonc.2021.743077] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2021] [Accepted: 10/01/2021] [Indexed: 12/11/2022] Open
Abstract
MicroRNAs (miRNAs) consist of a large family of small, non-coding RNAs with the ability to result in gene silencing post-transcriptionally. With recent advances in research technology over the past several years, the physiological and pathological potentials of miRNAs have been gradually uncovered. MiR-149-5p, a conserved miRNA, was found to regulate physiological processes, such as inflammatory response, adipogenesis and cell proliferation. Notably, increasing studies indicate miR-149-5p may act as an important regulator in solid tumors, especially cancers in reproductive system and digestive system. It has been acknowledged that miR-149-5p can function as an oncogene or tumor suppressor in different cancers, which is achieved by controlling a variety of genes expression and adjusting downstream signaling pathway. Moreover, the levels of miR-149-5p are influenced by several newly discovered long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs). However, there is blank about systematic function and mechanism of miR-149-5p in human cancers. In this review, we firstly summarize the present comprehension of miR-149-5p at the molecular level, its vital role in tumor initiation and progression, as well as its potential roles in monitoring diverse reproductive and digestive malignancies.
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Affiliation(s)
- Fu-jia Ren
- Department of Pharmacy, Hangzhou Women’s Hospital (Hangzhou Maternity and Child Health Care Hospital), Hangzhou, China
| | - Yao Yao
- Department of Pharmacy, Women’s Hospital School of Medicine, Zhejiang University, Hangzhou, China
| | - Xiao-yu Cai
- Department of Clinical Pharmacology, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yu-ting Cai
- Department of Pharmacy, Hangzhou Women’s Hospital (Hangzhou Maternity and Child Health Care Hospital), Hangzhou, China
| | - Qian Su
- Department of Pharmacy, Hangzhou Women’s Hospital (Hangzhou Maternity and Child Health Care Hospital), Hangzhou, China
| | - Guo-ying Fang
- Department of Pharmacy, Hangzhou Women’s Hospital (Hangzhou Maternity and Child Health Care Hospital), Hangzhou, China
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22
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Zhang K, Liu H, Yu M, Zhao H, Yang N, Bi X, Sun L, Lin R, Lü G. Upregulated LINC01667 Expression Is Correlated With Poor Prognosis in Hepatocellular Carcinoma. Front Oncol 2021; 11:650173. [PMID: 34458133 PMCID: PMC8397520 DOI: 10.3389/fonc.2021.650173] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Accepted: 07/12/2021] [Indexed: 12/25/2022] Open
Abstract
The development of hepatocellular carcinoma (HCC) is a complex pathological process. Long intergenic non–protein-coding RNA 1667 (LINC01667, also known as MGC38584) plays an oncogenic role in several human cancers; however, its functional role in HCC tumorigenesis remains unknown. Here, we first evaluated the gene expression levels of LINC01667 in HCC using data from The Cancer Genome Atlas and Gene Expression Profiling Interactive Analysis (GEPIA) databases. We then elucidated the association between LINC01667 gene expression levels and the survival rates of patients with HCC. We detected the effect of LINC01667 on the malignant phenotypes (cell proliferation, migration, invasion and apoptosis etc.) and the MAPK and PI3K/AKT/mTOR signaling pathways of HepG2, SMMC-7721 and HUH7 cells. We also analyzed the sensitivity of HepG2, SMMC-7721 and HUH7 with different expression levels of LINC01667 to anti-HCC drugs in vitro. Based on data from the aforementioned databases and our experiments in vitro, we found that LINC01667 was overexpressed in HCC, and that patients with high LINC01667 levels had a remarkably poor overall survival rate. In addition, inhibition of LINC01667 expression suppressed the proliferation, migration and invasion of HepG2 and SMMC-7721 cells and promoted their apoptosis in vitro. In contrast, overexpression of LINC01667 promoted the proliferation, migration and invasion of HUH7 cells and suppressed their apoptosis in vitro. ChIRP-seq (chromatin isolation by RNA purification) showed that LINC01667 bound to MEG3, and downregulated the expression of MEG3. In addition, western blotting showed that LINC01667 could activate the NF-κB pathway to promote cancer progression. In conclusion, we report that LINC01667 is an important oncogene in HCC and may be used as a potential diagnostic and prognostic biomarker of HCC.
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Affiliation(s)
- Kainan Zhang
- State Key Laboratory of Pathogenesis, Prevention, and Treatment of Central Asian High Incidence Diseases, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China.,Graduate Academy, Xinjiang Medical University, Urumqi, China
| | - Hui Liu
- State Key Laboratory of Pathogenesis, Prevention, and Treatment of Central Asian High Incidence Diseases, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Mengsi Yu
- Department of Clinical Laboratory, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Hui Zhao
- Department of Clinical Laboratory, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Ning Yang
- State Key Laboratory of Pathogenesis, Prevention, and Treatment of Central Asian High Incidence Diseases, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Xiaojuan Bi
- State Key Laboratory of Pathogenesis, Prevention, and Treatment of Central Asian High Incidence Diseases, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Li Sun
- State Key Laboratory of Pathogenesis, Prevention, and Treatment of Central Asian High Incidence Diseases, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Renyong Lin
- State Key Laboratory of Pathogenesis, Prevention, and Treatment of Central Asian High Incidence Diseases, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Guodong Lü
- State Key Laboratory of Pathogenesis, Prevention, and Treatment of Central Asian High Incidence Diseases, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China.,College of Pharmacy, Xinjiang Medical University, Urumqi, China
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23
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Long Non-coding RNAs: Potential Players in Cardiotoxicity Induced by Chemotherapy Drugs. Cardiovasc Toxicol 2021; 22:191-206. [PMID: 34417760 DOI: 10.1007/s12012-021-09681-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Accepted: 07/24/2021] [Indexed: 10/20/2022]
Abstract
One of the most important side effects of chemotherapy is cardiovascular complications, such as cardiotoxicity. Many factors are involved in the pathogenesis of cardiotoxicity; one of the most important of which is long non-coding RNAs (lncRNAs). lncRNA has 200-1000 nucleotides. It is involved in important processes such as cell proliferation, regeneration and apoptosis; today it is used as a prognostic and diagnostic factor. A, various drugs by acting on lncRNAs can affect cells. Therefore, by accurately identifying IncRNAs function, we can play an effective role in preventing the development of cardiotoxicity-induced chemotherapy drugs, and use them as a therapeutic strategy to improve clinical symptoms and increase patient survival.
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24
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Li F, Sun X, Liu Q, Liu X, Zhang J. Long Noncoding RNA MIR100HG Knockdown Attenuates Hepatocellular Carcinoma Progression by Regulating MicroRNA-146b-5p/Chromobox 6. Gastroenterol Res Pract 2021; 2021:6832518. [PMID: 34381502 PMCID: PMC8352691 DOI: 10.1155/2021/6832518] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Revised: 07/08/2021] [Accepted: 07/14/2021] [Indexed: 02/07/2023] Open
Abstract
PURPOSE Hepatocellular carcinoma (HCC) accounts for approximately ninety percent of primary liver cancer. This study attempted to investigate the effects of the long noncoding RNA MIR100HG (MIR100HG) in HCC and the underlying molecular mechanism. MATERIALS AND METHODS qRT-PCR was implemented to analyze the expression of MIR100HG, microRNA-146b-5p (miR-146b-5p), and Chromobox 6 (CBX6). The correlation between MIR100HG and clinicopathological features of HCC patients was assessed. Additionally, the effects of MIR100HG knockdown on HCC cell viability, migration, and invasion were explored. The interactions among MIR100HG, miR-146b-5p, and CBX6 were confirmed. Furthermore, rescue experiments were conducted to investigate whether MIR100HG knockdown modulates HCC cell behaviors through modulating the miR-146b-5p/CBX6 axis. RESULTS The expression of MIR100HG and CBX6 was enhanced, while miR-146b-5p was inhibited in HCC cells. High MIR100HG expression was positively associated with the TNM tumor stage and Edmondson-Steiner grading in HCC patients. MIR100HG knockdown considerably reduced the HCC cell viability, migration, and invasion. In addition, MIR100HG directly targeted miR-146b-5p, and miR-146b-5p directly targeted CBX6 in HCC cells. Moreover, miR-146b-5p suppression or CBX6 elevation evidently rescued the suppressed viability, migration, and invasion of HCC cells caused by MIR100HG knockdown. CONCLUSIONS Knockdown of MIR100HG inhibited the viability, migration, and invasion of HCC cells by targeting the miR-146b-5p/CBX6 axis, offering a potential therapeutic target for HCC therapy.
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Affiliation(s)
- Fushun Li
- Department of Hepatobiliary Surgery, Wei Fang Yi Du Central Hospital, No. 4318, South Linglong Mountain Road, Qingzhou County, Weifang City, Shandong Province 262500, China
| | - Xianghua Sun
- Department of Hepatobiliary Surgery, Wei Fang Yi Du Central Hospital, No. 4318, South Linglong Mountain Road, Qingzhou County, Weifang City, Shandong Province 262500, China
| | - Qing Liu
- Department of Hepatobiliary Surgery, Wei Fang Yi Du Central Hospital, No. 4318, South Linglong Mountain Road, Qingzhou County, Weifang City, Shandong Province 262500, China
| | - Xilu Liu
- Department of Hepatobiliary Surgery, Wei Fang Yi Du Central Hospital, No. 4318, South Linglong Mountain Road, Qingzhou County, Weifang City, Shandong Province 262500, China
| | - Jia Zhang
- Health Care Department I, Weifang People's Hospital, No. 151, Guangwen Street, Kuiwen District, Weifang City, Shandong Province 261041, China
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25
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Hu X, Zhu H, Shen Y, Zhang X, He X, Xu X. The Role of Non-Coding RNAs in the Sorafenib Resistance of Hepatocellular Carcinoma. Front Oncol 2021; 11:696705. [PMID: 34367979 PMCID: PMC8340683 DOI: 10.3389/fonc.2021.696705] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2021] [Accepted: 06/28/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death. Sorafenib is approved by the U.S. Food and Drug Administration to be a first-line chemotherapy agent for patients with advanced HCC. A portion of advanced HCC patients can benefit from the treatment with sorafenib, but many patients ultimately develop sorafenib resistance, leading to a poor prognosis. The molecular mechanisms of sorafenib resistance are sophisticated and indefinite. Notably, non-coding RNAs (ncRNAs), which include long ncRNAs (lncRNAs), microRNAs (miRNAs) and circular RNAs (circRNAs), are critically participated in the occurrence and progression of tumors. Moreover, growing evidence has suggested that ncRNAs are crucial regulators in the development of resistance to sorafenib. Herein, we integrally and systematically summarized the molecular mechanisms and vital role of ncRNAs impact sorafenib resistance of HCC, and ultimately explored the potential clinical administrations of ncRNAs as new prognostic biomarkers and therapeutic targets for HCC.
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Affiliation(s)
- Xinyao Hu
- Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, China.,Cancer Center, Renmin Hospital of Wuhan University, Wuhan, China
| | - Hua Zhu
- Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, China
| | - Yang Shen
- Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, China.,Cancer Center, Renmin Hospital of Wuhan University, Wuhan, China
| | - Xiaoyu Zhang
- Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, China.,Cancer Center, Renmin Hospital of Wuhan University, Wuhan, China
| | - Xiaoqin He
- Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, China.,Cancer Center, Renmin Hospital of Wuhan University, Wuhan, China
| | - Ximing Xu
- Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, China.,Cancer Center, Renmin Hospital of Wuhan University, Wuhan, China
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26
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Huang H, Peng J, Yi S, Ding C, Ji W, Huang Q, Zeng S. Circular RNA circUBE2D2 functions as an oncogenic factor in hepatocellular carcinoma sorafenib resistance and glycolysis. Am J Transl Res 2021; 13:6076-6086. [PMID: 34306346 PMCID: PMC8290719] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2020] [Accepted: 03/14/2021] [Indexed: 06/13/2023]
Abstract
Circular RNAs (circRNAs) have been reported to regulate the hepatocellular carcinoma (HCC) chemoresistance and tumor progression by regulating gene expression. However, the underlying molecular mechanisms of HCC sorafenib resistance regulated by circRNAs remain unclear. Here, higher expression of circUBE2D2 was directly associated with low survival rate in HCC patients. Functional experiments showed that circUBE2D2 promoted the glycolysis (Warburg effect) and sorafenib resistance in vitro, and knockdown of circUBE2D2 repressed the tumor growth in vivo. Mechanistically, circUBE2D2 was predominantly localized in the cytoplasm and sponged miR-889-3p, which in turn targeted the 3'-UTR of LDHA mRNA. Therefore, circUBE2D2 exerted an oncogenic role through miR-889-3p/LDHA axis. In conclusion, these findings demonstrate that circUBE2D2 accelerated the HCC glycolysis and sorafenib resistance via circUBE2D2/miR-889-3p/LDHA axis, which provides a novel approach for HCC treatment.
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Affiliation(s)
- Hai Huang
- Department of Hepatobiliary Surgery, Guangxi Medical University Affiliated Wuming HospitalNanning 530199, China
| | - Jian Peng
- Hepatobiliary and Enteral Surgery Research Center, Xiangya Hospital of Central South UniversityChangsha 410008, China
| | - Shijian Yi
- Department of General Surgery, Shenzhen University Affiliated General HospitalShenzhen 518055, China
| | - Chengmin Ding
- Department of Hepatobiliary Surgery, The First affiliated Hospital of South China UniversityHengyang 421001, China
| | - Wei Ji
- Department of Hepatobiliary Surgery, Guangxi Medical University Affiliated Wuming HospitalNanning 530199, China
| | - Qiangsong Huang
- Department of Hepatobiliary Surgery, Guangxi Medical University Affiliated Wuming HospitalNanning 530199, China
| | - Suna Zeng
- Department of Hepatobiliary Surgery, Guangxi Medical University Affiliated Wuming HospitalNanning 530199, China
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27
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The Possible Role of Cancer Stem Cells in the Resistance to Kinase Inhibitors of Advanced Thyroid Cancer. Cancers (Basel) 2020; 12:cancers12082249. [PMID: 32796774 PMCID: PMC7465706 DOI: 10.3390/cancers12082249] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2020] [Revised: 08/03/2020] [Accepted: 08/10/2020] [Indexed: 02/06/2023] Open
Abstract
Target therapy with various kinase inhibitors (KIs) has been extended to patients with advanced thyroid cancer, but only a subset of these compounds has displayed efficacy in clinical use. However, after an initial response to KIs, dramatic disease progression occurs in most cases. With the discovery of cancer stem cells (CSCs), it is possible to postulate that thyroid cancer resistance to KI therapies, both intrinsic and acquired, may be sustained by this cell subtype. Indeed, CSCs have been considered as the main drivers of metastatic activity and therapeutic resistance, because of their ability to generate heterogeneous secondary cell populations and survive treatment by remaining in a quiescent state. Hence, despite the impressive progress in understanding of the molecular basis of thyroid tumorigenesis, drug resistance is still the major challenge in advanced thyroid cancer management. In this view, definition of the role of CSCs in thyroid cancer resistance may be crucial to identifying new therapeutic targets and preventing resistance to anti-cancer treatments and tumor relapse. The aim of this review is to elucidate the possible role of CSCs in the development of resistance of advanced thyroid cancer to current anti-cancer therapies and their potential implications in the management of these patients.
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