Expression of MicroRNA-448 and SIRT1 and Prognosis of Obese Type 2 Diabetic Mellitus Patients After Laparoscopic Bariatric Surgery

Abstract

Background/Aims: This study sought to investigate the expression and prognostic value of peripheral blood microRNA-448 (miR-448) and its target gene SIRT1 after laparoscopic bariatric surgery in obese type 2 diabetic mellitus (T2DM) patients. Methods: Obese T2DM patients were selected and treated with laparoscopic bariatric surgery. Enzyme-linked immunosorbent assay (ELISA) was used to measure SIRT1 protein expression. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was employed to determine the mRNA expression of the related gene. Endothelial progenitor cells (EPCs) were grouped into blank, negative control (NC), miR-448 mimic, miR-448 inhibitor, siRNA-SIRT1 and miR-448 inhibitor + siRNA-SIRT1 groups. Transwell assays and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays were applied to determine cell invasion and cell viability. A tube formation assay and an adherence test were utilized to assess the angiogenic and adhesive capacities of the cells. Results: In peripheral blood, the expression of miR-448 was reduced, whereas the mRNA and protein expression of SIRT1 was increased after surgery compared to before surgery. miR-448 expression was lower and mRNA and protein expression of SIRT1 was higher in the effective group than in the ineffective group after surgery. SIRT1 is a target gene of miR-448. miR-448 can suppress viability and invasion, and it reflects the angiogenic and adhesive capacity of EPCs and the protein expression of relative genes in EPCs through targeting SIRT1. Conclusion: The results demonstrated that miR-448 and its target gene SIRT1 can serve as prognostic indicators for obese T2DM patients after laparoscopic bariatric surgery.

Suppression of TLR4 by miR-448 is involved in Diabetic development via regulating Macrophage polarization

“…[34,35] MiR-448 was recently found to reduce in peripheral blood of T2D patients after laparoscopic bariatric surgery and overexpressed miR-448 suppressed the viability and invasion of circulating endothelial progenitor cells through targeting SIRT1. [36] In contrast to TLR4, our data showed that miR-448 was significantly decreased in T2D mice-derived macrophages. More importantly, miR-448 was identified as the potential miRNA interacting with TLR4 3 0 -UTR by bioinformatics predictions, and this forecast result was demonstrated by our data of dual-luciferase gene reporter assay.…”

“…As small, non‐protein coding RNA, miR‐448 played an essential role in cellular functions, including proliferation, migration, and apoptosis through regulating the expression of targeted mRNAs . MiR‐448 was recently found to reduce in peripheral blood of T2D patients after laparoscopic bariatric surgery and overexpressed miR‐448 suppressed the viability and invasion of circulating endothelial progenitor cells through targeting SIRT1 . In contrast to TLR4, our data showed that miR‐448 was significantly decreased in T2D mice‐derived macrophages.…”

Obesity-Related Epigenetic Changes After Bariatric Surgery

“…Only one very recent study focused on epigenomics and bariatric surgery efficacy. Even though it should be verified in an independent study, this work suggests that miR-448 and its target gene SIRT1 could serve as prognostic indicators for obese T2D patients after laparoscopic bariatric surgery (114). That study was performed using peripheral blood obtained from obese T2D patients.…”

miR‑448 promotes progression of non‑small‑cell lung cancer via targeting SIRT1

“…Particularly, miR-138 was demonstrated to suppress NSCLC cell growth, metastasis and autophagy via targeting SIRT1 (24). Although a previous study investigated miR-448 and SIRT1 in patients with diabetes mellitus (30), their role in cancer cells, particularly NSCLC cells, remains unknown. In clinical samples, the expression of SIRT1 was higher in tumor tissues and its levels were inversely correlated with miR-448 levels.…”