Background: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.Methods and Results: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 ofLINC01138, 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.Conclusions:These findings identify MP60 as a potential biomarker and therapeutic target in HCC, linking its oncogenic effects to EMT modulation and tumor progression.
背景：由非编码RNA编码的微肽在多种细胞功能中扮演关键角色。尽管已有若干微肽被证实与肝细胞癌（HCC）相关，但其具体作用机制尚未完全阐明。本研究鉴定出一种与HCC进展密切相关的保守微肽MP60。 方法与结果：通过分析癌症基因组图谱（TCGA）数据集，我们评估了在HCC中表达显著变化的长链非编码RNA（lncRNA）的编码潜力。研究发现，LINC01138的转录本ENST0000614292显示出最高的编码潜力，其编码一种推测由60个氨基酸组成的微肽，我们将其命名为MP60，并证实了MP60在HCC组织中的表达及其核定位特征。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能够调控上皮-间质转化（EMT）过程。功能分析表明，MP60促进细胞增殖和迁移，同时降低细胞黏附能力，并在体内实验中转化为增强的肿瘤发生能力。值得注意的是，MP60在HCC组织中表达显著上调，且与患者不良预后相关。 结论：这些发现确立了MP60作为HCC潜在生物标志物和治疗靶点的重要性，并将其促癌效应与EMT调控及肿瘤进展联系起来。
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