High glucose regulates ERp29 in hepatocellular carcinoma by LncRNA MEG3-miRNA 483-3p pathway

Abstract

AimsBlood glucose dysregulation is an adverse factor in the prognosis of hepatocellular carcinoma (HCC). Endoplasmic reticulum (ER) is thought to be crucial component in the development of cancer and diabetes. This study aimed to investigate the mechanisms of poor outcomes in HCC patients with diabetes. Main methodsER protein 29 (ERp29) was predicted by proteomics, immunohistochemistry, Western blot, Cell Counting Kit-8 (CCK-8) and cell scratch test were used to identify the expression and biological effects of ERp29 under high glucose (HG) in HCC cells. Bioinformatics found a competing endogenous RNAs (ceRNAs) regulatory network between microRNA-483-3p (miR-483-3p) and Long noncoding RNA (LncRNA MEG3), the above methods also were used to identify their expression, biological effects and their roles of HG on regulation of REp29 in HCC cells, Dual-luciferase reporter assay was carried out to study the interaction of ERp29 with miR-483-3p and miR-483-3p with MEG3. Key findingsHG upregulated miR-483-3p expression in HCC cells and miR-483-3p overexpression suppressed ERp29 expression and also increased HCC cell proliferation and migration. Furthermore, we found that MEG3 was decreased in HCC cells incubated in medium with high glucose and knockdown of MEG3 downregulated ERp29 expression. Bioinformatics analysis found that MEG3 mediated its protective effects via binding to miR-483-3p. SignificanceOverall, our study established a novel regulatory network of LncRNA MEG3/miR483-3p/ERp29 in HCC which may be helpful in better understanding the effect of high glucose on poor prognosis of HCC and in exploring new diagnostic and therapeutic tools for managing HCC in patients with diabetes.