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Hao B, Liu Y, Wang B, Wu H, Chen Y, Zhang L. Hepatitis B surface antigen: carcinogenesis mechanisms and clinical implications in hepatocellular carcinoma. Exp Hematol Oncol 2025; 14:44. [PMID: 40141002 PMCID: PMC11938626 DOI: 10.1186/s40164-025-00642-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2025] [Accepted: 03/11/2025] [Indexed: 03/28/2025] Open
Abstract
Liver cancer is the third leading cause of death globally, with hepatitis B virus (HBV) infection being identified as the primary risk factor for its development. The occurrence of HBV-related hepatocellular carcinoma (HCC) is attributed to various mechanisms, such as chronic inflammation and liver cell regeneration induced by the cytotoxic immune response triggered by the virus, abnormal activation of oncogenes arising from HBV DNA insertion mutations, and epigenetic alterations mediated by viral oncoproteins. The envelope protein of the HBV virus, known as hepatitis B surface antigen (HBsAg), is a key indicator of increased risk for developing HCC in HBsAg-positive individuals. The HBsAg seroclearance status is found to be associated with recurrence in HCC patients undergoing hepatectomy. Additional evidence indicates that HBsAg is essential to the entire process of tumor development, from initiation to advancement, and acts as an oncoprotein involved in accelerating tumor progression. This review comprehensively analyzes the extensive effects and internal mechanisms of HBsAg during the various stages of the initiation and progression of HCC. Furthermore, it highlights the importance and potential applications of HBsAg in the realms of HCC early diagnosis and personalized therapeutic interventions. An in-depth understanding of the molecular mechanism of HBsAg in the occurrence and development of HCC is provided, which is expected to develop more precise and efficient strategies for the prevention and management of HCC in the future.
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Affiliation(s)
- Bingyan Hao
- Hepatic Surgery Center, Institute of Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Yachong Liu
- Hepatic Surgery Center, Institute of Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Bohan Wang
- Hepatic Surgery Center, Institute of Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Haofeng Wu
- Hepatic Surgery Center, Institute of Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Yan Chen
- Department of Paediatrics, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
| | - Lei Zhang
- Department of Hepatobiliary Surgery, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Shanxi Tongji Hospital, Tongji Medical College, Shanxi Medical University, Huazhong University of Science and Technology, Taiyuan, 030032, China.
- Department of Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
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Abam F, Ghorbian S. The dual role of LncRNAs in hepatocellular carcinoma: Friend and foe. GASTROENTEROLOGY & ENDOSCOPY 2024; 2:186-195. [DOI: 10.1016/j.gande.2024.06.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/15/2025]
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3
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Ding W, Xi S, Gao K, Weng D, Xu S, Huang G, Yu M, Yue H, Wang J. Clinical significance of LINC02532 in hepatitis B virus-associated hepatocellular carcinoma and its regulatory effect on tumor progression. Clin Res Hepatol Gastroenterol 2024; 48:102403. [PMID: 38901567 DOI: 10.1016/j.clinre.2024.102403] [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: 04/24/2024] [Revised: 06/14/2024] [Accepted: 06/18/2024] [Indexed: 06/22/2024]
Abstract
BACKGROUND AND AIM Long non-coding RNAs (lncRNAs) play an important role in tumor progression, including in hepatocellular carcinoma (HCC) induced by hepatitis B virus (HBV). Therefore, the aim of this study was to investigate the role of LINC02532 in HCC, mainly for diagnostic prognostic value and cellular function, as well as mechanistic aspects. METHODS Initially, GEO and VirBase databases were used to screen for aberrant lncRNAs in HBV-HCC.Then, HBV-HCC persons followed up in our center were retrospectively studied to investigate the diagnostic, prognostic value of LINC02532 in HBV-HCC. Subsequently, the role of LINC02532 in HBV-HCC was measured using cellular function assay methods and possible mechanisms were analyzed in conjunction with bioinformatic predictive science. RESULTS LINC02532 was a lncRNA abnormally expressed in HBV-HCC. LINC02532 was significantly up-regulated in the expression level in HBV-HCC tissues compared with normal tissues from patients. Moreover, LINC02532 could distinguish HBV-HCC and predict the prognosis of HBV-HCC. In vitro experiments showed that LINC02532 could regulate miR-455-3p and promote the malignant characterization of HBV-HCC cells. CHEK2 was a target gene of miR-455-3p. CONCLUSIONS The prognosis and diagnosis of HBV-HCC can rely on the expression of LINC02532. LINC02532 was important for further progression of HBV-HCC, by moderating miR-455-3p/CHEK2.
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Affiliation(s)
- Wei Ding
- Department of Gastroenterology, PLA Naval Medical Center, No.338 Huaihai West Road, Changning District, Shanghai 200052, China
| | - Sujuan Xi
- Department of Gastroenterology, PLA Naval Medical Center, No.338 Huaihai West Road, Changning District, Shanghai 200052, China
| | - Kewei Gao
- Department of Gastroenterology, PLA Naval Medical Center, No.338 Huaihai West Road, Changning District, Shanghai 200052, China
| | - Danping Weng
- Department of Gastroenterology, PLA Naval Medical Center, No.338 Huaihai West Road, Changning District, Shanghai 200052, China
| | - Sheng Xu
- Department of Gastroenterology, PLA Naval Medical Center, No.338 Huaihai West Road, Changning District, Shanghai 200052, China
| | - Guoping Huang
- Department of Gastroenterology, PLA Naval Medical Center, No.338 Huaihai West Road, Changning District, Shanghai 200052, China
| | - Min Yu
- Department of Radiotherapy, PLA Naval Medical Center, No.338 Huaihai West Road, Changning District, Shanghai 200052, China
| | - Haiyan Yue
- Department of Gastroenterology, PLA Naval Medical Center, No.338 Huaihai West Road, Changning District, Shanghai 200052, China.
| | - Jianguo Wang
- Department of Radiotherapy, PLA Naval Medical Center, No.338 Huaihai West Road, Changning District, Shanghai 200052, China.
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Adugna A, Muche Y, Melkamu A, Jemal M, Belew H, Amare GA. Current updates on the molecular and genetic signals as diagnostic and therapeutic targets for hepatitis B virus-associated hepatic malignancy. Heliyon 2024; 10:e34288. [PMID: 39100497 PMCID: PMC11295980 DOI: 10.1016/j.heliyon.2024.e34288] [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: 12/22/2023] [Revised: 05/28/2024] [Accepted: 07/07/2024] [Indexed: 08/06/2024] Open
Abstract
Liver cancer caused by the hepatitis B virus (HBV) is the third most common cancer-related cause of death worldwide. Early detection of HBV-caused hepatic tumors increases the likelihood of a successful cure. Molecular and genetic signals are becoming more and more recognized as possible indicators of HBV-associated hepatic malignancy and of how well a treatment is working. As a result, we have discussed the current literature on molecular and genetic sensors, including extracellular vesicle microRNAs (EV-miRNAs), long non-coding circulating RNAs (lncRNAs), extracellular vesicles (EVs), and cell free circulating DNA (cfDNA), for the diagnosis and forecasting of HBV-related hepatic cancer. Extracellular vesicle microRNAs such as miR-335-5p, miR-172-5p, miR-1285-5p, miR-497-5p, miR-636, miR-187-5p, miR-223-3p, miR-21, miR-324-3p, miR-210-3p, miR-718, miR-122, miR-522, miR-0308-3p, and miR-375 are essential for the posttranscriptional regulation of oncogenes in hepatic cells as well as the epigenetic modulation of many internal and external signaling pathways in HBV-induced hepatic carcinogenesis. LncRNAs like lnc01977, HULC (highly up-regulated in liver cancer), MALAT1 (metastasis-associated lung adenocarcinoma transcript 1), and HOTAIR (hox transcript antisense intergenic RNA) have been demonstrated to control hepatic-tumors cell growth, relocation, encroachment, and cell death resiliency. They are also becoming more and more involved in immune tracking, hepatic shifting, vasculature oversight, and genomic destabilization. EVs are critical mediators involved in multiple aspects of liver-tumors like angiogenesis, immunology, tumor formation, and the dissemination of malignant hepatocytes. Furthermore, cfDNA contributes to signals associated with tumors, including mutations and abnormal epigenetic changes during HBV-related hepatic tumorigenesis.
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Affiliation(s)
- Adane Adugna
- Medical Laboratory Sciences, College of Health Sciences, Debre Markos University, Debre Markos, Ethiopia
| | - Yalew Muche
- Medical Laboratory Sciences, College of Health Sciences, Debre Markos University, Debre Markos, Ethiopia
| | - Abateneh Melkamu
- Medical Laboratory Sciences, College of Health Sciences, Debre Markos University, Debre Markos, Ethiopia
| | - Mohammed Jemal
- Department of Biomedical Sciences, School of Medicine, College of Health Sciences, Debre Markos University, Debre Markos, Ethiopia
| | - Habtamu Belew
- Medical Laboratory Sciences, College of Health Sciences, Debre Markos University, Debre Markos, Ethiopia
| | - Gashaw Azanaw Amare
- Medical Laboratory Sciences, College of Health Sciences, Debre Markos University, Debre Markos, Ethiopia
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Shojaeian A, Nakhaie M, Amjad ZS, Boroujeni AK, Shokri S, Mahmoudvand S. Leveraging metformin to combat hepatocellular carcinoma: its therapeutic promise against hepatitis viral infections. JOURNAL OF CANCER METASTASIS AND TREATMENT 2024. [DOI: 10.20517/2394-4722.2023.147] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
Hepatocellular carcinoma (HCC) is categorized among the most common primary malignant liver cancer and a primary global cause of death from cancer. HCC tends to affect males 2-4 times more than females in many nations. The main factors that raise the incidence of HCC are chronic liver diseases, hepatotropic viruses like hepatitis B (HBV) and C (HCV), non-alcoholic fatty liver disease, exposure to toxins like aflatoxin, and non-alcoholic steatohepatitis (NASH). Among these, hepatitis B and C are the most prevalent causes of chronic hepatitis globally. Metformin, which is made from a naturally occurring compound called galegine, derived from the plant Galega officinalis (G. officinalis ), has been found to exhibit antitumor effects in a wide range of malignancies, including HCC. In fact, compared to patients on sulphonylureas or insulin, studies have demonstrated that metformin treatment significantly lowers the risk of HCC in patients with chronic liver disease. This article will first describe the molecular mechanism of hepatitis B and C viruses in the development of HCC. Then, we will provide detailed explanations about metformin, followed by a discussion of the association between metformin and hepatocellular carcinoma caused by the viruses mentioned above.
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Hu J, Zhang L, Zheng X, Wang G, Chen X, Hu Z, Chen Y, Wang X, Gu M, Hu S, Liu X, Jiao X, Peng D, Liu X. Long noncoding RNA #61 exerts a broad anti-influenza a virus effect by its long arm rings. Antiviral Res 2023; 215:105637. [PMID: 37196902 DOI: 10.1016/j.antiviral.2023.105637] [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: 02/23/2023] [Revised: 05/11/2023] [Accepted: 05/14/2023] [Indexed: 05/19/2023]
Abstract
Emerging evidence has demonstrated the critical role of long noncoding RNAs (lncRNAs) in regulating gene expression. However, the functional significance and mechanisms underlying influenza A virus (IAV)-host lncRNA interactions are still elusive. Here, we identified a functional lncRNA, LncRNA#61, as a broad anti-IAV factor. LncRNA#61 is highly upregulated by different subtypes of IAV, including human H1N1 virus and avian H5N1 and H7N9 viruses. Furthermore, nuclear-enriched LncRNA#61 can translocate from the nucleus to the cytoplasm soon after IAV infection. Forced LncRNA#61 expression dramatically impedes viral replication of various subtypes of IAV, including human H1N1 virus and avian H3N2/N8, H4N6, H5N1, H6N2/N8, H7N9, H8N4, H10N3, H11N2/N6/N9 viruses. Conversely, abolishing LncRNA#61 expression substantially favored viral replication. More importantly, LncRNA#61 delivered by the lipid nanoparticle (LNP)-encapsulated strategy shows good performance in restraining viral replication in mice. Interestingly, LncRNA#61 is involved in multiple steps of the viral replication cycle, including virus entry, viral RNA synthesis and the virus release period. Mechanistically, the four long ring arms of LncRNA#61 mainly mediate its broad antiviral effect and contribute to its inhibition of viral polymerase activity and nuclear aggregation of key polymerase components. Therefore, we defined LncRNA#61 as a potential broad-spectrum antiviral factor for IAV. Our study further extends our understanding of the stunning and unanticipated biology of lncRNAs as well as their close interaction with IAV, providing valuable clues for developing novel broad anti-IAV therapeutics targeting host lncRNAs.
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Affiliation(s)
- Jiao Hu
- Animal Infectious Disease Laboratory, School of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou, Jiangsu, China; Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agri-food Safety and Quality, Ministry of Agriculture of China (26116120), Yangzhou University, Yangzhou, China
| | - Lei Zhang
- Animal Infectious Disease Laboratory, School of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou, Jiangsu, China; Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agri-food Safety and Quality, Ministry of Agriculture of China (26116120), Yangzhou University, Yangzhou, China
| | - Xinxin Zheng
- Animal Infectious Disease Laboratory, School of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou, Jiangsu, China; Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agri-food Safety and Quality, Ministry of Agriculture of China (26116120), Yangzhou University, Yangzhou, China
| | - Guoqing Wang
- Animal Infectious Disease Laboratory, School of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou, Jiangsu, China; Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agri-food Safety and Quality, Ministry of Agriculture of China (26116120), Yangzhou University, Yangzhou, China
| | - Xia Chen
- Animal Infectious Disease Laboratory, School of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou, Jiangsu, China; Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agri-food Safety and Quality, Ministry of Agriculture of China (26116120), Yangzhou University, Yangzhou, China
| | - Zenglei Hu
- Animal Infectious Disease Laboratory, School of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, China; Joint International Research Laboratory of Agriculture and Agri-Product Safety, The Ministry of Education of China, Yangzhou University, Yangzhou, China; Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agri-food Safety and Quality, Ministry of Agriculture of China (26116120), Yangzhou University, Yangzhou, China
| | - Yu Chen
- Animal Infectious Disease Laboratory, School of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou, Jiangsu, China; Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agri-food Safety and Quality, Ministry of Agriculture of China (26116120), Yangzhou University, Yangzhou, China
| | - Xiaoquan Wang
- Animal Infectious Disease Laboratory, School of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou, Jiangsu, China; Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agri-food Safety and Quality, Ministry of Agriculture of China (26116120), Yangzhou University, Yangzhou, China
| | - Min Gu
- Animal Infectious Disease Laboratory, School of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou, Jiangsu, China; Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agri-food Safety and Quality, Ministry of Agriculture of China (26116120), Yangzhou University, Yangzhou, China
| | - Shunlin Hu
- Animal Infectious Disease Laboratory, School of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou, Jiangsu, China; Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agri-food Safety and Quality, Ministry of Agriculture of China (26116120), Yangzhou University, Yangzhou, China
| | - Xiaowen Liu
- Animal Infectious Disease Laboratory, School of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou, Jiangsu, China; Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agri-food Safety and Quality, Ministry of Agriculture of China (26116120), Yangzhou University, Yangzhou, China
| | - Xinan Jiao
- Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agri-food Safety and Quality, Ministry of Agriculture of China (26116120), Yangzhou University, Yangzhou, China; Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou, China
| | - Daxin Peng
- Animal Infectious Disease Laboratory, School of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou, Jiangsu, China; Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agri-food Safety and Quality, Ministry of Agriculture of China (26116120), Yangzhou University, Yangzhou, China
| | - Xiufan Liu
- Animal Infectious Disease Laboratory, School of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou, Jiangsu, China; Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agri-food Safety and Quality, Ministry of Agriculture of China (26116120), Yangzhou University, Yangzhou, China.
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Yan LR, Liu AR, Jiang LY, Wang BG. Non-coding RNA and hepatitis B virus-related hepatocellular carcinoma: A bibliometric analysis and systematic review. Front Med (Lausanne) 2022; 9:995943. [PMID: 36203765 PMCID: PMC9530602 DOI: 10.3389/fmed.2022.995943] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2022] [Accepted: 08/23/2022] [Indexed: 11/18/2022] Open
Abstract
Objectives A bibliometric analysis for non-coding RNA and hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) was performed to describe international research status and visualize the research scope and emerging trends over the last two decades on this topic. Materials and methods Research data of non-coding RNA and HBV-related HCC were retrieved and extracted from the Web of Science Core Collection (WoSCC) database from 1 January 2003 to 13 June 2022 and then analyzed by means of bibliometric methods. A total of 1,036 articles published in this field were assessed for specific characteristics, including the year of publication, journal, author, institution, country/region, references, and keywords. VOSviewer was employed to perform co-authorship, co-occurrence, and co-citation analyses accompanied by constructing a visual network. Results Overall, 1,036 reports on non-coding RNA and HBV-related HCC from 2003 to 2022 were retrieved from WoSCC. The publication has gradually increased during the last two decades with 324 journals involved. Most research records (748 publications and 23,184 citations) were concentrated in China. A co-occurrence cluster analysis for the top 100 keywords was performed and four clusters were generated: (1) non-coding RNA as a molecular marker for the diagnosis and prognosis of HBV-related HCC; (2) dysregulation of non-coding RNA by hepatitis B virus X protein (HBx); (3) non-coding RNA affecting the biological behaviors of HBV-related HCC; and (4) epidemiological study for the effects of non-coding RNA on the risk of HBV-related HCC. Conclusion The publications and citations involved in non-coding RNA and HBV-related HCC have increased over the last two decades associated with many countries, institutions, and authors. Our study revealed current development trends, global cooperation models, basic knowledge, research hotspots, and emerging frontiers in this field.
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Affiliation(s)
- Li-rong Yan
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Hospital of China Medical University, Key Laboratory of Cancer Etiology and Prevention, China Medical University, Liaoning Provincial Education Department, Shenyang, China
| | - Ao-ran Liu
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Hospital of China Medical University, Key Laboratory of Cancer Etiology and Prevention, China Medical University, Liaoning Provincial Education Department, Shenyang, China
| | - Li-yue Jiang
- Tangdu Hospital of the Fourth Military Medical University, Xi’an, China
| | - Ben-gang Wang
- Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Hospital of China Medical University, Key Laboratory of Cancer Etiology and Prevention, China Medical University, Liaoning Provincial Education Department, Shenyang, China
- Department of Hepatobiliary Surgery, Institute of General Surgery, The First Hospital of China Medical University, Shenyang, China
- *Correspondence: Ben-gang Wang,
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Giordo R, Gulsha R, Kalla S, Calin GA, Lipovich L. LncRNA-Associated Genetic Etiologies Are Shared between Type 2 Diabetes and Cancers in the UAE Population. Cancers (Basel) 2022; 14:3313. [PMID: 35884374 PMCID: PMC9313416 DOI: 10.3390/cancers14143313] [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] [Received: 03/16/2022] [Revised: 04/22/2022] [Accepted: 05/06/2022] [Indexed: 12/13/2022] Open
Abstract
Numerous epidemiological studies place patients with T2D at a higher risk for cancer. Many risk factors, such as obesity, ageing, poor diet and low physical activity, are shared between T2D and cancer; however, the biological mechanisms linking the two diseases remain largely unknown. The advent of genome wide association studies (GWAS) revealed large numbers of genetic variants associated with both T2D and cancer. Most significant disease-associated variants reside in non-coding regions of the genome. Several studies show that single nucleotide polymorphisms (SNPs) at or near long non-coding RNA (lncRNA) genes may impact the susceptibility to T2D and cancer. Therefore, the identification of genetic variants predisposing individuals to both T2D and cancer may help explain the increased risk of cancer in T2D patients. We aim to investigate whether lncRNA genetic variants with significant diabetes and cancer associations overlap in the UAE population. We first performed an annotation-based analysis of UAE T2D GWAS, confirming the high prevalence of variants at or near non-coding RNA genes. We then explored whether these T2D SNPs in lncRNAs were relevant to cancer. We highlighted six non-coding genetic variants, jointly reaching statistical significance in T2D and cancer, implicating a shared genetic architecture between the two diseases in the UAE population.
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Affiliation(s)
- Roberta Giordo
- College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai 505055, United Arab Emirates; (R.G.); (R.G.); (S.K.)
| | - Rida Gulsha
- College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai 505055, United Arab Emirates; (R.G.); (R.G.); (S.K.)
| | - Sarah Kalla
- College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai 505055, United Arab Emirates; (R.G.); (R.G.); (S.K.)
| | - George A. Calin
- Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;
- Center for RNA Interference and Non-Coding RNAs, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Leonard Lipovich
- College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai 505055, United Arab Emirates; (R.G.); (R.G.); (S.K.)
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