Novel insights into small open reading frame-encoded micropeptides in hepatocellular carcinoma: A potential breakthrough

Traditionally, non -coding RNAs (ncRNAs) are regarded as a class of RNA transcripts that lack encoding capability; however, advancements in technology have revealed that some ncRNAs contain small open reading frames (sORFs) that are capable of encoding micropeptides of approximately 150 amino acids in length. sORF-encoded micropeptides (SEPs) have emerged as intriguing entities in hepatocellular carcinoma (HCC) research, shedding light on this previously unexplored realm. Recent studies have highlighted the regulatory functions of SEPs in the occurrence and progression of HCC. Some SEPs exhibit inhibitory effects on HCC, but others facilitate its development. This discovery has revolutionized the landscape of HCC research and clinical management. Here, we introduce the concept and characteristics of SEPs, summarize their associations with HCC, and elucidate their carcinogenic mechanisms in HCC metabolism, signaling pathways, cell proliferation, and metastasis. In addition, we propose a step-by-step workflow for the investigation of HCC-associated SEPs. Lastly, we discuss the challenges and prospects of applying SEPs in the diagnosis and treatment of HCC. This review aims to facilitate the discovery, optimization, and clinical application of HCC-related SEPs, inspiring the development of early diagnostic, individualized, and precision therapeutic strategies for HCC.