Li Chencheng, Hong Xiu, Setrerrahmane Sarra, Sun Xiaoyi, Zhang Xue, Xu Hanmei
Jiangsu Province Engineering Research Center of Synthetic Peptide Drug Discovery and Evaluation, China Pharmaceutical University, Nanjing 210009, China.
Nanjing Anji Biotechnology Co., Ltd., Nanjing 210033, China.
Cancers (Basel). 2025 Sep 7;17(17):2932. doi: 10.3390/cancers17172932.
Micropeptides, encoded by non-coding RNAs, play a pivotal role in various cellular functions. While several micropeptides have already been linked to HCC, their roles remain incompletely understood. Our study identifies MP60, a conserved micropeptide strongly associated with HCC progression. By analyzing The Cancer Genome Atlas (TCGA) dataset, we assessed the coding potential of long non-coding RNAs (lncRNAs) with significant expression changes in HCC. Our findings reveal that ENST0000614292, a transcript of , exhibited the highest coding potential, encoding a putative 60-amino-acid micropeptide, which we have named MP60 and confirmed the expression of MP60 in HCC tissues, with a nuclear localization. MP60 directly interacts with RNA-binding motif protein 10 (RBM10) and downregulates its expression. Additionally, MP60 modulates EMT. Functional analyses demonstrated that MP60 promotes cellular proliferation and migration, while reducing cellular adhesion, translated by enhanced tumorigenesis in vivo. Notably, MP60 expression is markedly increased in HCC tissues and is associated with a poorer prognosis. These findings identify MP60 as a potential biomarker and therapeutic target in HCC, linking its oncogenic effects to EMT modulation and tumor progression.
由非编码RNA编码的微小肽在各种细胞功能中起着关键作用。虽然已有几种微小肽与肝癌相关联,但其作用仍未完全了解。我们的研究鉴定出MP60,这是一种与肝癌进展密切相关的保守微小肽。通过分析癌症基因组图谱(TCGA)数据集,我们评估了在肝癌中表达有显著变化的长链非编码RNA(lncRNA)的编码潜力。我们的研究结果表明,ENST0000614292(一种……的转录本)表现出最高的编码潜力,编码一种推测的60个氨基酸的微小肽,我们将其命名为MP60,并证实了MP60在肝癌组织中的表达,其定位于细胞核。MP60直接与RNA结合基序蛋白10(RBM10)相互作用并下调其表达。此外,MP60调节上皮-间质转化(EMT)。功能分析表明,MP60促进细胞增殖和迁移,同时降低细胞黏附,这在体内通过增强肿瘤发生得以体现。值得注意的是,MP60在肝癌组织中的表达显著增加,且与较差的预后相关。这些研究结果确定MP60为肝癌的潜在生物标志物和治疗靶点,将其致癌作用与EMT调节和肿瘤进展联系起来。