Sex‐specific analysis of microRNA profiles in HBV‐associated cirrhosis by small RNA‐sequencing

Abstract Liver cirrhosis represents an advanced stage of chronic liver disease and is associated with significant morbidity, mortality, and risk of cancer development. While sex disparity of liver diseases has been observed, understanding at a genetic level awaits more thorough investigation. In thi...

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Main Authors: Kristy Kwan‐Shuen Chan, Kwan‐Yung Au, Wai‐Ching Fung, Cheuk‐Yan Wong, Albert Chi‐Yan Chan, Regina Cheuk‐Lam Lo
Format: Article
Language:English
Published: Wolters Kluwer Health/LWW 2022-12-01
Series:Hepatology Communications
Online Access:https://doi.org/10.1002/hep4.2096
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author Kristy Kwan‐Shuen Chan
Kwan‐Yung Au
Wai‐Ching Fung
Cheuk‐Yan Wong
Albert Chi‐Yan Chan
Regina Cheuk‐Lam Lo
author_facet Kristy Kwan‐Shuen Chan
Kwan‐Yung Au
Wai‐Ching Fung
Cheuk‐Yan Wong
Albert Chi‐Yan Chan
Regina Cheuk‐Lam Lo
author_sort Kristy Kwan‐Shuen Chan
collection DOAJ
description Abstract Liver cirrhosis represents an advanced stage of chronic liver disease and is associated with significant morbidity, mortality, and risk of cancer development. While sex disparity of liver diseases has been observed, understanding at a genetic level awaits more thorough investigation. In this study, we performed a sex‐specific analysis of the microRNA (miR) profiles in hepatitis B virus (HBV)–associated cirrhosis by small RNA‐sequencing using clinical tissue samples. Potential associated signaling pathways, downstream gene targets, and upstream regulators were highlighted by computational prediction analyses based on the differentially expressed miRs (DEmiRs). From our results, deregulation of miRs in cirrhosis showed a marked difference between males and females by the degree and pattern. Sixty‐five (64 up‐regulated, 1 down‐regulated) and 12 (6 up‐regulated, 6 down‐regulated) DEmiRs were found in males and females, respectively, when compared with their respective control group. A number of DEmiRs were only observed in one sex but not the other. In addition, 26 DEmiRs were identified between cirrhosis female and cirrhosis male groups. Fatty acid biosynthesis pathway, extracellular matrix–receptor interaction, p53 signaling, Hippo signaling, tumor necrosis factor signaling, the forkhead box O signaling, as well as gene targets ribosomal protein S27 like, methyl CpG binding protein 2, and estrogen receptor 1, may contribute to the pathogenesis and biological behavior of cirrhosis in a sex‐specific manner. Analysis of the Cancer Genome Atlas data set suggested a role of sex‐specific DEmiRs in multistep hepatocarcinogenesis. Conclusion: Our findings illustrate that miR profiles in HBV‐associated cirrhosis are distinct between the males and females and suggest a potential role of sex‐specific biomarkers and molecular mechanisms in disease development and progression.
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spelling doaj.art-3f3c0dfce4df469f95a5bd79d19918082023-09-02T10:27:04ZengWolters Kluwer Health/LWWHepatology Communications2471-254X2022-12-016123473348610.1002/hep4.2096Sex‐specific analysis of microRNA profiles in HBV‐associated cirrhosis by small RNA‐sequencingKristy Kwan‐Shuen Chan0Kwan‐Yung Au1Wai‐Ching Fung2Cheuk‐Yan Wong3Albert Chi‐Yan Chan4Regina Cheuk‐Lam Lo5Department of Pathology, School of Clinical Medicine The University of Hong Kong Hong Kong ChinaDepartment of Pathology, School of Clinical Medicine The University of Hong Kong Hong Kong ChinaDepartment of Pathology, School of Clinical Medicine The University of Hong Kong Hong Kong ChinaDepartment of Pathology, School of Clinical Medicine The University of Hong Kong Hong Kong ChinaDepartment of Surgery, School of Clinical Medicine The University of Hong Kong Hong Kong ChinaDepartment of Pathology, School of Clinical Medicine The University of Hong Kong Hong Kong ChinaAbstract Liver cirrhosis represents an advanced stage of chronic liver disease and is associated with significant morbidity, mortality, and risk of cancer development. While sex disparity of liver diseases has been observed, understanding at a genetic level awaits more thorough investigation. In this study, we performed a sex‐specific analysis of the microRNA (miR) profiles in hepatitis B virus (HBV)–associated cirrhosis by small RNA‐sequencing using clinical tissue samples. Potential associated signaling pathways, downstream gene targets, and upstream regulators were highlighted by computational prediction analyses based on the differentially expressed miRs (DEmiRs). From our results, deregulation of miRs in cirrhosis showed a marked difference between males and females by the degree and pattern. Sixty‐five (64 up‐regulated, 1 down‐regulated) and 12 (6 up‐regulated, 6 down‐regulated) DEmiRs were found in males and females, respectively, when compared with their respective control group. A number of DEmiRs were only observed in one sex but not the other. In addition, 26 DEmiRs were identified between cirrhosis female and cirrhosis male groups. Fatty acid biosynthesis pathway, extracellular matrix–receptor interaction, p53 signaling, Hippo signaling, tumor necrosis factor signaling, the forkhead box O signaling, as well as gene targets ribosomal protein S27 like, methyl CpG binding protein 2, and estrogen receptor 1, may contribute to the pathogenesis and biological behavior of cirrhosis in a sex‐specific manner. Analysis of the Cancer Genome Atlas data set suggested a role of sex‐specific DEmiRs in multistep hepatocarcinogenesis. Conclusion: Our findings illustrate that miR profiles in HBV‐associated cirrhosis are distinct between the males and females and suggest a potential role of sex‐specific biomarkers and molecular mechanisms in disease development and progression.https://doi.org/10.1002/hep4.2096
spellingShingle Kristy Kwan‐Shuen Chan
Kwan‐Yung Au
Wai‐Ching Fung
Cheuk‐Yan Wong
Albert Chi‐Yan Chan
Regina Cheuk‐Lam Lo
Sex‐specific analysis of microRNA profiles in HBV‐associated cirrhosis by small RNA‐sequencing
Hepatology Communications
title Sex‐specific analysis of microRNA profiles in HBV‐associated cirrhosis by small RNA‐sequencing
title_full Sex‐specific analysis of microRNA profiles in HBV‐associated cirrhosis by small RNA‐sequencing
title_fullStr Sex‐specific analysis of microRNA profiles in HBV‐associated cirrhosis by small RNA‐sequencing
title_full_unstemmed Sex‐specific analysis of microRNA profiles in HBV‐associated cirrhosis by small RNA‐sequencing
title_short Sex‐specific analysis of microRNA profiles in HBV‐associated cirrhosis by small RNA‐sequencing
title_sort sex specific analysis of microrna profiles in hbv associated cirrhosis by small rna sequencing
url https://doi.org/10.1002/hep4.2096
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