GRHPR, targeted by miR-138-5p, inhibits the proliferation and metastasis of hepatocellular carcinoma through PI3K/AKT signaling pathway

Abstract

Abstract Background Hepatocellular carcinoma (HCC) is one of the most aggressive cancers. The present study aimed to investigate the effects of GRHPR on the proliferation and metastasis of HCC and to identify the miRNA targeting GRHPR to understand the underlying mechanism of miR-138-5p/GRHPR on HCC proliferation and metastasis. Methods The expression levels of GRHPR and miR-138-5p were detected in HCC tissues and cells. Bioinformatic analysis and dual-luciferase reporter assay were carried out to confirm that GRHPR was a target gene of miR-138-5p. HCC cell lines overexpressing GRHPR were established to detect the roles of GRHPR in HCC cell proliferation, migration and invasion. The biological function of miR-138-5p targeting to GRHPR in HCC cell lines was also evaluated. The xenograft mouse model was established to investigate the functions of GRHPR in vivo. Results GRHPR was markedly downregulated in human HCC samples, whereas miR-138-5p was upregulated in HCC samples. The expression of GRHPR was regulated by miR-138-5p in HCC cell lines. HCC cell proliferation, migration and invasion could be suppressed by GRHPR overexpression and GRHPR exerted an anti-tumor effect in a xenograft mouse model. However, the inhibition of GRHPR by miR-138-5p promoted the proliferation and invasive properties of HCC cells. MiR-138-5p could regulate the phosphorylation levels of PI3K and AKT related to the phosphatidylinositol signaling pathway via inhibiting GRHPR expression. Conclusions This study suggests that GRHPR may play a significant role in HCC and its function is regulated by miR-138-5p.