The long non-coding RNA Linc-GALH promotes hepatocellular carcinoma metastasis via epigenetically regulating Gankyrin

摘要

Hepatocellular carcinoma (HCC) is the most prevalent subtype of liver cancer, and it is characterized by high rate of metastasis and recurrence. Recent studies have boosted our understanding that Gankyrin contributes to both of these pathological properties, but the mechanisms underlying its aberrant regulation are poorly understood. Recently, many long noncoding RNAs (lncRNAs) have been reported to be involved in regulating the expression of oncogenes and anti-oncogenes through various mechanisms. Here, using transcriptome microarray analysis, we identified a long intergenic noncoding RNA termed Linc-GALH that was highly expressed and concordance with Gankyrin expression in HCC. In addition, we revealed that Linc-GALH was an independent unfavorable prognostic indicator for HCC, followed functional experiments showed that Linc-GALH promoted HCC cells migration and invasion in vitro, and enhanced lung metastasis ability of HCC cells in vivo. Mechanistically, we found that Linc-GALH could regulate the expression of Gankyrin through controlling the methylation status of Gankyrin by adjusting the ubiquitination status of DNMT1 in HCC. Collectively, our results demonstrated the role and functional mechanism of Linc-GALH in HCC, and indicated that Linc-GALH may act as a prognostic biomarker and potential therapeutic target for HCC.