Yu SM, Zhang M, Li SL, Pei SY, Wu L, Hu XW, Duan YK. Long noncoding RNA semaphorin 6A-antisense RNA 1 reduces hepatocellular carcinoma by promoting semaphorin 6A mRNA degradation. World J Gastroenterol 2025; 31(13): 102527 [DOI: 10.3748/wjg.v31.i13.102527]
Corresponding Author of This Article
Yan-Kun Duan, PhD, Department of Infectious Diseases, Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Changsha 410008, Hunan Province, China. ykduan@csu.edu.cn
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastroenterol. Apr 7, 2025; 31(13): 102527 Published online Apr 7, 2025. doi: 10.3748/wjg.v31.i13.102527
Long noncoding RNA semaphorin 6A-antisense RNA 1 reduces hepatocellular carcinoma by promoting semaphorin 6A mRNA degradation
Song-Man Yu, Min Zhang, Sha-Lin Li, Si-Ya Pei, Li Wu, Xing-Wang Hu, Yan-Kun Duan
Song-Man Yu, Min Zhang, Sha-Lin Li, Li Wu, Yan-Kun Duan, Department of Infectious Diseases, Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
Si-Ya Pei, Department of Blood Transfusion, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
Xing-Wang Hu, Department of Infectious Diseases, Hunan Key Laboratory of Viral Hepatitis, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
Author contributions: Yu SM contributed to supervision, statistical analysis and drafting the manuscript; Yu SM and Zhang M contributed to Investigation; Li SL contributed to financial support; Zhang M, Li SL, and Pei SY contributed to sample collection; Wu L and Hu XW contributed to technical support; Duan YK contributed to conceptualization, reviewing and editing the manuscript, and financial support.
Supported by Natural Science Foundation of Hunan Province, No. 2021JJ41048 and No. S2019JJQNJJ2012; and Changsha Natural Science Foundation, No. kq2208400.
Institutional review board statement: This study was conducted in accordance with the Declaration of Helsinki (revised in 2013) and approved by the Ethics Committee of the Xiangya Hospital (No. 202009883).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: All data used and/or analyzed in this study are available from the corresponding author on reasonable request.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Yan-Kun Duan, PhD, Department of Infectious Diseases, Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Changsha 410008, Hunan Province, China. ykduan@csu.edu.cn
Received: October 21, 2024 Revised: February 13, 2025 Accepted: March 6, 2025 Published online: April 7, 2025 Processing time: 163 Days and 17.7 Hours
Abstract
BACKGROUND
Hepatocellular carcinoma (HCC) is a prevalent malignant tumor with a poor prognosis, which is often associated with chronic hepatitis B virus infection in China. Our previous study has shown that long non-coding RNA semaphorin 6A-antisense RNA 1 (SEMA6A-AS1) was significantly downregulated in hepatitis B virus-related HCC and associated with poor prognosis.
AIM
To explore the underlying mechanism of SEMA6A-AS1 in HCC progression.
METHODS
The expression levels of SEMA6A-AS1 and SEMA6A were detected using quantitative polymerase chain reaction, immunohistochemistry and Western blot. A growth curve, colony formation, wound-healing and transwell (with or without Matrigel) assays were respectively performed to assess the proliferation, migration and invasion abilities of HCC cells. Cell cycle and apoptosis assays were performed by flow cytometry. To investigate the potential mechanism underpinning SEMA6A-AS1, we utilized tagged RNA affinity purification, dual luciferase reporter assay and immunofluorescence.
RESULTS
Downregulation of SEMA6A-AS1 in HCC was negatively correlated with SEMA6A protein expression. SEMA6A was upregulated in HCC and correlated with high alpha-fetoprotein level, high Edmondson-Steiner grade and poor prognosis. SEMA6A-AS1 significantly inhibited the proliferation, migration and invasion of HCC cells by combining with SEMA6A mRNA and promoting its degradation. SEMA6A protein promoted the proliferation, migration and invasion of HCC cells by regulating the actin cytoskeleton.
CONCLUSION
Our findings suggest that SEMA6A-AS1 can inhibit HCC progression through decreasing SEMA6A expression by promoting its mRNA degradation. SEMA6A-AS1 may be a prognostic biomarker and therapeutic target for HCC.
Core Tip: This study investigated the association of semaphorin 6A-antisense RNA 1 (SEMA6A-AS1) and SEMA6A with clinical features and prognosis of hepatocellular carcinoma (HCC), and their functional implications in HCC cell proliferation, migration and invasion. Further investigation has revealed that SEMA6A-AS1 can reverse the progression of HCC by decreasing SEMA6A expression through mRNA stabilization and actin cytoskeleton regulation. These findings expand the understanding of molecular mechanisms of SEMA6A-AS1 in HCC progression and provide novel therapeutic targets for HCC.
