High-Throughput Proteomics Reveals a Novel Small Open Reading Frame-Encoded Peptide That Promotes Hepatocellular Carcinoma Invasion and Migration

Long noncoding RNAs (lncRNAs) are closely associated with tumor development, and increasing evidence suggests that small open reading frame (smORF) within lncRNAs also have the capability to encode smORF-encoded peptides (SEPs). Here, we thoroughly uncovered the SEP expression profile of hepatocellular carcinoma (HCC) from tumor and adjacent nontumor tissues of 154 HCC patients using high-throughput mass spectrometry (MS). A total of 208 SEPs were identified, with no significant difference in abundance and stability compared with coding region proteins. Notably, the peptide encoded by LINC01007 (LINC01007-33AA) was significantly upregulated in HCC tissues (p < 0.05) and could serve as an independent risk factor affecting prognosis (HR [95% CI]: 1.31[1.01–1.7]). This endogenous peptide was further confirmed at both the mRNA and protein levels, and its overexpression significantly enhances the invasion and migration of HCC cells. These findings highlight the potential of MS-based methods to identify novel noncoding sequence encoded functional peptides associated with tumor progression.