Gene amplification-driven lncRNA SNHG6 promotes tumorigenesis via epigenetically suppressing p27 expression and regulating cell cycle in non-small cell lung cancer

Long non-coding RNAs (lncRNAs) have been validated to play essential roles in non-small cell lung carcinoma (NSCLC) progression. In this study, through systematically screening GSE33532 and GSE29249 from Gene Expression Omnibus (GEO) database and bioinformatics analysis, we found the significant upregulation of SNHG6 in NSCLC. The activation of SNHG6 was driven by copy number amplification and high expression of SNHG6 indicated a poor prognosis. Functionally, the knockdown of SNHG6 inhibited NSCLC cell proliferation, migration, and suppressed the G1/S transition of the cell cycle. SNHG6 overexpression had the opposite effects. Mechanically, SNHG6 recruited EZH2 to the promoter region of p27 and increased H3K27me3 enrichment, thus epigenetically repressing the expression of p27, regulating the cell cycle, and promoting tumorigenesis of NSCLC. SNHG6 silencing restrained tumor growth in vivo and suppressed the expressions of cell cycle-related proteins in the G1/S transition. In conclusion, our study uncovered a novel mechanism of SNHG6 activation and its function. SNHG6 can be considered a potential target for the diagnosis and treatment of NSCLC in the future.

Automated summary

In this study, the significant upregulation of SNHG6 in non-small cell lung carcinoma (NSCLC) was identified through data screening and bioinformatics analysis. Functionally, SNHG6 was found to promote NSCLC cell proliferation and migration by regulating the cell cycle. Mechanically, SNHG6 epigenetically repressed the expression of p27 through recruiting EZH2, thereby promoting tumorigenesis. These findings highlight the importance of SNHG6 as a potential diagnostic and therapeutic target for NSCLC.