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

Abstract

AIMS:

Blood 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 METHODS:

ER 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 FINDINGS:

HG 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.

SIGNIFICANCE:

Overall, 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.

• Authors: Xin Li, Ting Cheng, Yuan He, Saijun Zhou, Yao Wang, Kai Zhang, Pei Yu
• Journal: Life sciences (Life Sci) Vol. 232 Pg. 116602 (Sep 01 2019) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 31251997 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• Blood Glucose
• ERP29 protein, human
• Heat-Shock Proteins
• MEG3 non-coding RNA, human
• MIRN483 microRNA, human
• MicroRNAs
• RNA, Long Noncoding
• Glucose

Topics

• Aged
• Aged, 80 and over
• Blood Glucose (metabolism)
• Carcinoma, Hepatocellular (blood, genetics, metabolism, pathology)
• Cell Line, Tumor
• Cell Proliferation (physiology)
• Diabetes Mellitus (blood, metabolism, pathology)
• Endoplasmic Reticulum (physiology)
• Female
• Glucose (metabolism)
• HEK293 Cells
• Heat-Shock Proteins (metabolism)
• Hep G2 Cells
• Humans
• Liver Neoplasms (blood, genetics, metabolism, pathology)
• Male
• MicroRNAs (genetics, metabolism)
• Middle Aged
• Prognosis
• RNA, Long Noncoding (genetics, metabolism, physiology)
• Signal Transduction