HMGA1 promotes hepatocellular carcinoma proliferation, migration, and regulates cell cycle via miR-195-5p

HMGA1 has been reported to be aberrantly expressed and correlate with the poor prognosis of many carcinomas. This study aimed to investigate the clinical significance and molecular mechanism of HMGA1 as a tumor-suppressing gene in hepatocellular carcinoma (HCC). Analysis of TCGA dataset by TANRIC website and R2 platform, we found that HMGA1 expression was significantly higher in HCC tissues compared to that in normal liver tissues and was associated with Edmondson grade. Patients with highly expressed HMGA1 had worse overall survival. Gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes analysis showed the potential relationships between HMGA1 and other genes in HCC. We also demonstrated that the downregulation of HMGA1 dramatically suppressed the proliferation and migration of HCC cells. Furthermore, ectopic expression of HMGA1 blocked G0/G1 to S transition. Subsequent investigation characterized HMGA1 as a direct target of miR-195-5p, and miR-195-5p downregulation abrogated the effect of HMGA1 on HCC proliferation, migration, and cell cycle arrest. In addition, we also demonstrated that miR-195-5p downregulation abrogated the effect of HMGA1 on HCC growth in vivo. Taken together, our data provide strong evidence that HMGA1 promotes HCC and is negatively regulated by the tumor-suppressor, miR-195-5p.

Automated summary

This study investigated the clinical significance and molecular mechanisms of HMGA1 as a tumor-suppressing gene in hepatocellular carcinoma (HCC). The results showed that HMGA1 was significantly higher in HCC tissues and correlated with poor prognosis. Gene analysis revealed potential relationships between HMGA1 and other genes in HCC. Downregulation of HMGA1 suppressed HCC cell proliferation and migration, and blocked cell cycle progression. Further investigation identified miR-195-5p as a direct regulator of HMGA1, and its downregulation abolished the effects of HMGA1 on HCC. The study provides strong evidence for the role of HMGA1 in promoting HCC and its negative regulation by miR-195-5p.