Deciphering the methylation landscape of long noncoding RNAs in hepatocellular carcinoma: a focus on LINC00942.

Background: Conduct a comprehensive genome-wide methylomic analysis of long noncoding RNA (lncRNA) genes in hepatocellular carcinoma (HCC) and identify specific lncRNAs for subsequent functional validation.

Methods: We conducted a methylation microarray analysis on 11 HCC samples alongside adjacent non-tumor tissue specimens. This analysis was integrated with The Cancer Genome Atlas data and the Gene Expression Omnibus for a comprehensive methylomic evaluation. Following this, a LASSO retrospective analysis was employed to develop a prognostic model for HCC, utilizing the methylation levels of specific lncRNA genes. Ultimately, LINC00942 was identified as a significant candidate within the model, and its biological effects in HCC cells were investigated through both in vitro and in vivo experiments. Additionally, potential downstream target genes of LINC00942 were elucidated using western blot analysis.

Results: Genome-wide hypomethylation and CpG island hypermethylation within lncRNA genes were observed in HCC. Furthermore, a prognostic model utilizing the methylation levels of five specific lncRNA genes has demonstrated high accuracy in predicting the prognosis of patients diagnosed with HCC. LINC00942, an identified lncRNA within the model, exhibits hypomethylation and elevated expression levels in HCC. Methylation within the promoter region has been shown to suppress its expression in HCC cells. Both in vivo and in vitro studies have demonstrated that the silencing of LINC00942 leads to a decrease in the proliferation, migration, and invasion of HCC cells. Flow cytometry analyses revealed a significant increase in cell cycle arrest and apoptosis in HCC cells following the knockdown of LINC00942. The result of western blot indicates that cyclin D1, CDK2, and BAX are probable downstream target molecules of LINC00942.

Conclusions: A substantial quantity of lncRNAs is transcriptionally modulated by methylation in HCC. The demethylation of LINC00942 within its promoter region facilitates the upregulation of LINC00942 expression, thereby contributing to its function as an oncogene in HCC.