Zhang Chao, Wang Xiaoxiao, Song Huangqin, Yuan Junlong, Zhang Xiaomin, Yuan Yiran, Wang Zhuangqiang, Lei Zhang, He Jiefeng
Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, 030032, China.
Linfen Central Hospital, LinFen, 041099, China.
Cell Biol Toxicol. 2024 Dec 21;41(1):9. doi: 10.1007/s10565-024-09959-1.
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.
The expression difference of LIMA1 in hepatocellular carcinoma, which was verified by 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.
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.
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.
肝细胞癌（HCC）被认为是全球最常见且致命的癌症之一，已引起研究人员的高度关注。在对多种癌症进行广泛研究后，LIMA1在肿瘤发生和癌症进展中的作用仍不明确。此外，LIMA1在HCC中的作用仍存在争议。
本研究通过TMT定量蛋白质组学、免疫组织化学、蛋白质印迹法以及TCGA数据库，对LIMA1在肝细胞癌中的表达差异进行了研究。通过Transwell、cck8、成球实验等实验证明，LIMA1对肝细胞癌的迁移、增殖、干性等方面有显著影响。此外，通过RNA测序和蛋白质印迹法揭示了LIMA1对wnt-β-连环蛋白/河马通路的影响，并通过COIP验证了LIMA1与β-连环蛋白之间的关系。最后，通过蛋白质印迹法、放线菌素D和MeRip实验进一步验证了m6A修饰对LIMA1的影响。
在HCC组织和几种HCC细胞系中，LIMA1表达水平相对较高。LIMA1正向调节肝细胞癌的侵袭、迁移、增殖和干性，沉默LIMA1可抑制HCC细胞在裸鼠中的致瘤能力。此外，研究表明LIMA1可对wnt-β-连环蛋白/河马通路产生影响。沉默β-连环蛋白可抑制由LIMA1介导的肝细胞癌细胞的侵袭、迁移、增殖和干性。最后，进一步证实肝细胞癌细胞中LIMA1的激活是由于依赖于METTL3的m6-甲基腺苷甲基化。
在HCC中，LIMA1作为肿瘤促进因子发挥作用，并参与WNT-β-连环蛋白和河马信号通路，影响肿瘤细胞的特性。LIMA1的表达受METTL3介导的m6A修饰调控，导致其在HCC中高表达。我们的研究为HCC的检测和治疗提供了一个有希望的靶点。
