M6A modification-mediated LIMA1 promotes the progression of hepatocellular carcinoma through the wnt-βcatenin/Hippo pathway

Sep 21, 2026

Hepatocellular carcinoma (HCC) remains one of the most common and lethal cancers worldwide, and the role of LIMA1 in tumorigenesis is still disputed. This study examines how LIMA1 expression differs in HCC and evaluates its effects on migration, proliferation, stemness, and tumorigenic potential. Mechanistic work links LIMA1 to the WNT-β-catenin/Hippo pathway, including dependencies on β-catenin, while identifying METTL3-dependent m6A methylation on LIMA1 as the regulatory basis for its high expression. Findings support LIMA1 as a tumor-promoting factor and a potential diagnostic/therapeutic target for HCC.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages21

Reading Time53 min

AccessFree to download

Abstract

Background

Methods

Experimental approaches

Results

Conclusions

Introduction

LIMA1 and its expression in cancer

Wnt and Hippo signaling in HCC

Cell Biol Toxicol (2025) 41:9 [https://doi.org/10.1007/s10565-024-09959-1](https://doi.org/10.1007/s10565-024-09959-1) M6A modification‑mediated LIMA1 promotes the progression of hepatocellular carcinoma through the wnt‑βcatenin/Hippo pathway Chao Zhang · Xiaoxiao Wang · Huangqin Song · Junlong Yuan · Xiaomin Zhang · Yiran Yuan · Zhuangqiang Wang · Zhang Lei · Jiefeng He Received: 6 May 2024 / Accepted: 25 November 2024 © The Author(s) 2024 Abstract Background Hepatocellular carcinoma (HCC), considered as one of the most common and lethal cancers worldwide, has drawn significant attention from researchers.Extensively studied diverse cancers, the function of LIMA1 in tumorigenesis and cancer progression remains ambiguous.. Moreover, the role of LIMA1 in HCC remains controversial. Methods The expression difference of LIMA1 in hepatocellular carcinoma, which was verified by | Chao Zhang and Xiaoxiao Wang are co-first authors to this work. | | --- | | Supplementary Information The online version contains supplementary material available at [https://doi](https://doi). org/10.1007/s10565-024-09959-1. | C. Zhang · X. Wang · H. Song · J. Yuan · X. Zhang · Y. Yuan · Z. Wang · Z. Lei (*) · J. He (*) Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan 030032, China e-mail: [zhangl7803@126.com](zhangl7803@126.com) J. He e-mail: [jfhe@sxmu.edu.cn](jfhe@sxmu.edu.cn) [C. Zhang](C. Zhang) Linfen Central Hospital, LinFen 041099, China Z. Lei Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China TMT quantitative proteomics, immunohistochemistry, western blot, and the TCGA database, has been investigated in this study. Demonstrated by using transwell, cck8, sphere formation, and other experiments, the effects of LIMA1 on the migration, proliferation, stemness, and other aspects of hepatocellular carcinoma were significant. Moreover, the effect of LIMA1 on the wnt-βcatenin/Hippo pathway was revealed by using RNA sequencing and western blot, and the relationship between LIMA1 and βcatenin was verified by using COIP. Finally, the effect of m6a modification on LIMA1 was further verified using Western blotting, actinomycin D and MeRip experiments. Results In HCC tissues and several HCC cell lines, LIMA1 was expressed at a relatively high level. LIMA1 positively regulated the invasion, migration, proliferation and stemness of hepatocellular carcinoma, and silencing of LIMA1 inhibited the tumorigenic ability of HCC cells in nude mice. Moreover, it was shown that LIMA1 can have an impact on the wnt-β-catenin/Hippo pathway. And silencing β-catenin suppressed the invasion, migration, proliferation and stemness of hepatocellular carcinoma cells mediated by LIMA1 . Finally, it was further verified that the activation of LIMA1 in hepatocellular carcinoma cells is due to m6-methyladenosine methylation that is dependent on METTL3 . Conclusions In HCC, LIMA1 functions as a tumor promoter and engages with the WNT-β -catenin and Hippo signaling pathways,, affecting the characteristics of tumor cells. LIMA1 expression is regulated by METTL3-mediated m6A modification, leading to its high expression in HCC. Our research presents a hopeful objective for the detection and therapy of HCC. Keywords Hepatocellular carcinoma · LIMA1 · Cancer stem cells · WNT- β -catenin signaling · Hippo signaling pathways · M6A Introduction Primary liver cancer is an important public health issue worldwide, standing at the sixth position in terms of cancer prevalence and being the fourth major cause of cancer deaths globally(Sung et al. 2021 ; Yang and Heimbach 2020) . Hepatocellular carcinoma (HCC) serves as the leading histological form of primary liver neoplasm, accounting for roughly 70—80% of these malignant diseases (Llovet et al. 2021) . Despite the developments in clinical interventions in

FAQs

What role does LIMA1 play in hepatocellular carcinoma progression?

LIMA1 is expressed at relatively high levels in HCC tissues and cell lines, and it positively regulates invasion, migration, proliferation, and stemness. Silencing LIMA1 reduces tumorigenic ability of HCC cells in nude mice.

How does LIMA1 influence signaling pathways in HCC?

LIMA1 impacts the Wnt-β-catenin/Hippo pathway. Silencing β-catenin suppresses invasion, migration, proliferation, and stemness of HCC cells mediated by LIMA1.

What regulates LIMA1 expression in HCC?

LIMA1 activation is attributed to m6A methylation dependent on METTL3. METTL3-mediated m6A modification leads to higher LIMA1 expression in HCC.

Sep 21, 2026

Upload by Genevieve