Basic Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 7, 2025; 31(1): 101198
Published online Jan 7, 2025. doi: 10.3748/wjg.v31.i1.101198
Loss-of-function mutations of microRNA-142-3p promote ASH1L expression to induce immune evasion and hepatocellular carcinoma progression
Xing-Hui Yu, Yan Xie, Jian Yu, Kun-Ning Zhang, Zhou-Bo Guo, Di Wang, Zhao-Xian Li, Wei-Qi Zhang, Yu-Ying Tan, Li Zhang, Wen-Tao Jiang
Xing-Hui Yu, Kun-Ning Zhang, Zhao-Xian Li, Wei-Qi Zhang, Wen-Tao Jiang, School of Medicine, Nankai University, Tianjin 300192, China
Xing-Hui Yu, Yan Xie, Yu-Ying Tan, Wen-Tao Jiang, Tianjin Key Laboratory of Molecular Diagnosis and Treatment of Liver Cancer, Tianjin First Center Hospital, Tianjin 300192, China
Yan Xie, Li Zhang, Wen-Tao Jiang, Department of Liver Transplantation, Tianjin First Center Hospital, Tianjin 300192, China
Jian Yu, Zhou-Bo Guo, Di Wang, First Central Clinical School, Tianjin Medical University, Tianjin 300192, China
Author contributions: Yu XH, Xie Y, and Jiang WT conceived and designed the study; Yu XH, Yu J, Zhang KN, and Guo ZB performed the experimental part; Yu XH, Wang D and Li ZX contributed to data analysis; Yu XH wrote the paper; Zhang WQ, Zhang L, Tan YY, and Jiang WT reviewed and edited the manuscript; Jiang WT is the corresponding author; All authors have read and approved the final manuscript.
Supported by the Haihe Laboratory of Cell Ecosystem Innovation Fund, No. 22HHXBJC00001; and the Key Discipline Special Project of Tianjin Municipal Health Commission, No. TJWJ2022XK016.
Institutional review board statement: The research involving human participators were retrospected and approved by the Ethics Committee of Tianjin First Central Hospital, protocol number: YC-BY-LC-2023-038.
Institutional animal care and use committee statement: The animal experiment was approved by the Animal Experiment Ethics Committee of the Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, protocol number: IRM/2-IACUC-2408-027.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Data sharing statement: The authors confirm that the data supporting the findings of this study are available within the article and as its supplementary materials.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
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: Wen-Tao Jiang, MD, PhD, Chief Doctor, School of Medicine, Nankai University, No. 94 Weijin Road, Nankai District, Tianjin 300192, China. jiangwentao@nankai.edu.cn
Received: September 7, 2024
Revised: September 28, 2024
Accepted: November 14, 2024
Published online: January 7, 2025
Processing time: 93 Days and 7.9 Hours
Abstract
BACKGROUND

Hepatocellular carcinoma (HCC) has been a pervasive malignancy throughout the world with elevated mortality. Efficient therapeutic targets are beneficial to treat and predict the disease. Currently, the exact molecular mechanisms leading to the progression of HCC are still unclear. Research has shown that the microRNA-142-3p level decreases in HCC, whereas bioinformatics analysis of the cancer genome atlas database shows the ASH1L expression increased among liver tumor tissues. In this paper, we will explore the effects and mechanisms of microRNA-142-3p and ASH1L affect the prognosis of HCC patients and HCC cell bioactivity, and the association between them.

AIM

To investigate the effects and mechanisms of microRNA-142-3p and ASH1L on the HCC cell bioactivity and prognosis of HCC patients.

METHODS

In this study, we grouped HCC patients according to their immunohistochemistry results of ASH1L with pathological tissues, and retrospectively analyzed the prognosis of HCC patients. Furthermore, explored the roles and mechanisms of microRNA-142-3p and ASH1L by cellular and animal experiments, which involved the following experimental methods: Immunohistochemical staining, western blot, quantitative real-time-polymerase chain reaction, flow cytometric analysis, tumor xenografts in nude mice, etc. The statistical methods involved in this study contained t-test, one-way analysis of variance, the χ2 test, the Kaplan-Meier approach and the log-rank test.

RESULTS

In this study, we found that HCC patients with high expression of ASH1L possess a more recurrence rate as well as a decreased overall survival rate. ASH1L promotes the tumorigenicity of HCC and microRNA-142-3p exhibits reduced expression in HCC tissues and interacts with ASH1L through targeting the ASH1L 3′untranslated region. Furthermore, microRNA-142-3p promotes apoptosis and inhibits proliferation, invasion, and migration of HCC cell lines in vitro via ASH1L. For the exploration mechanism, we found ASH1L may promote an immunosuppressive microenvironment in HCC and ASH1L affects the expression of the cell junction protein zonula occludens-1, which is potentially relevant to the immune system.

CONCLUSION

Loss function of microRNA-142-3p induces cancer progression and immune evasion through upregulation of ASH1L in HCC. Both microRNA-142-3p and ASH1L can feature as new biomarker for HCC in the future.

Keywords: Hepatocellular carcinoma; MicroRNA-142-3p; ASH1L; Immune evasion; Tumor immune microenvironment; Apoptosis

Core Tip: This article mainly focuses on the new targets which may be beneficial to treat and predict hepatocellular carcinoma. We would like to shed light on the effects of microRNA-142-3p and ASH1L on the hepatocellular carcinoma cell bioactivity and prognosis of hepatocellular carcinoma patients. Based on the experiments, loss function of microRNA-142-3p induces cancer progression and immune evasion through upregulation of ASH1L in hepatocellular carcinoma. Both microRNA-142-3p and ASH1L can feature as new biomarker for hepatocellular carcinoma in the future. In-depth comprehensive research is indispensable to completely clarity the ASH1L pathology and relevant molecular mechanisms in hepatocellular carcinoma progression.