Regulation of the miR-19b-mediated SOCS6-JAK2/STAT3 pathway by lncRNA MEG3 is involved in high glucose-induced apoptosis in hRMECs

Abstract

Objective: Diabetic retinopathy (DR) is one of the most severe and common complications of diabetes mellitus. The present study aimed to investigate the molecular mechanism of MEG3, miR-19b and SOCS6 in human retinal microvascular endothelial cells (hRMECs) under high glucose conditions. Methods: HRMECs were cultured in 5 or 30 mM D-glucose medium. qRT-PCR and Western blotting were used to determine the mRNA expression and protein levels. MTT assay and flow cytometry analysis were performed to detect the viability and apoptosis of hRMECs, respectively. TNF-α, IL-6 and IL-1β levels in cell supernatants were detected by ELISA. The activity of caspase-3/7 was also determined. A luciferase reporter assay was performed to confirm the targeting relationship between miR-19b and SOCS6, as well as MEG3 and miR-19b. Results: Our study demonstrated that miR-19b was increased and SOCS6 was decreased in HG-induced hRMECs. Knockdown of SOCS6 inhibited cell viability and reversed the promotion of cell viability induced by knockdown of miR-19b. Additionally, miR-19b directly targeted and negatively regulated SOCS6. Moreover, miR-19b promoted the cell apoptosis rate and caspase-3/7 activity and increased inflammatory factors through the SOCS6-mediated JAK2/STAT3 signalling pathway. In addition, MEG3 attenuated HG-induced apoptosis of hRMECs by targeting the miR-19b/SOCS6 axis. Conclusion: These findings indicate that MEG3 inhibited HG-induced apoptosis and inflammation by regulating the miR-19b/SOCS6 axis through the JAK2/STAT3 signalling pathway in hRMECs. Thus, these findings might provide a new target for the treatment of DR.

Silencing LncRNA PVT1 Reverses High Glucose-Induced Regulation of the High Expression of PVT1 in HRMECs by Targeting miR-128-3p

“…Our results suggested that PVT1 had great potential as a diagnostic biomarker for patients with DR. The abnormal behavior of HRMECs has been confirmed to be closely associated with a variety of retinal vascular diseases and played an important role in DR [34]. Furthermore, the dysregulation of lncRNA can regulate the proliferation and migration of HRMECs in the high glucose environment, such as MALAT1 [35].…”

Erythropoietin Attenuates Experimental Contrast-Induced Nephrology: A Role for the Janus Kinase 2/Signal Transducer and Activator of Transcription 3 Signaling Pathway

“…To the best of our knowledge, no studies have investigated the role of JAK2/STAT3 signaling in CIN. It was reported that the phosphorylated activation of JAK2/STAT3 played a part in the induction of apoptosis, autophagy, inflammation, and oxidative stress and that the activation of the JAK2-STAT3 signaling pathway protected tissue against acute injury in some studies (35)(36)(37). In contrast, the renoprotective effect of curcumin in AKI caused by lipopolysaccharide (LPS) or severe acute pancreatitis may be associated with inflammation reduction mediated by suppression of JAK2/STAT3 signaling pathway (38,39).…”

miRNA, lncRNA and circRNA: Targeted Molecules Full of Therapeutic Prospects in the Development of Diabetic Retinopathy

“…Likewise, TPTEP1 can inhibit the phosphorylation and nuclear translocation of STAT3, thereby downregulating VEGFA mRNA and protein levels and hindering the formation of new blood vessels under HG conditions ( 68 ). MEG3 negatively regulates miR-19b to inhibit HG-induced inflammatory factors generated from HMRECs, caspase-3/7 and cell apoptosis ( 69 ). Therefore, reversing the expression level of lncRNAs under certain conditions may play a role in promoting the alleviation of DR.…”