A putative lncRNA RBM26-AS1-encoded micropeptide promotes colon cancer progression.

[BACKGROUND] The functional diversity and mechanistic complexity of long non-coding RNAs (lncRNAs) exert various regulatory roles in cancer, and they have traditionally been annotated as non-coding genes. Currently, the coding potential of lncRNAs is gradually being revealed; however, their validation and mechanisms of action in cancer remain largely unknown.

[METHODS] The expression, prognosis, and function of RBM26-AS1 in colon cancer were analyzed by bioinformatics, and its coding potential was predicted. The expression and localization of the RBM26-AS1 peptide were verified by constructing various fusion constructs, western blotting, and immunofluorescence. Cell proliferation and clonal formation experiments verified the functional effects of micropeptide on colon cancer cells. Co-immunoprecipitation (co-IP), mass spectrometry, and bioinformatic analysis were used to determine the possible mechanism of action of the micropeptide.

[RESULTS] The lncRNA RBM26-AS1 could encode two micropeptides with different relative molecular masses. The RBM26-AS1 peptide promotes colon cancer cell growth and colony formation. Mechanistically, the RBM26-AS1 peptide may play a role in enhancing nucleocytoplasmic transport and protein processing in the endoplasmic reticulum, which may be different from the function of lncRNA itself. The inhibition of the RBM26-AS1 peptide impairs the proliferation ability of colon cancer cells.

[CONCLUSIONS] A previously unknown micropeptide hidden in lncRNA RBM26-AS1 may contribute to colon cancer progression by enhancing nucleoplasmic transport and protein processing in the endoplasmic reticulum.