Glucose-induced microRNA-218 suppresses the proliferation and promotes the apoptosis of human retinal pigment epithelium cells by targeting RUNX2

Abstract

Objective: MicroRNA-218 (miR-218) critical for preventing the progression of numerous diseases, including diseases of the retinal pigment epithelium (RPE). However, the mechanism by which miR-218 regulates the PRE in humans remains largely unknown. Our study investigated the effects of glucose-induced miR-218 expression on human RPE cells (ARPE-19), as well as its targeted regulatory effect. Methods: The levels of miR-218 and runt-related transcription factor 2 (RUNX2) expression were investigated by RT-qPCR or Western blot assays. Cell viability and apoptosis were assessed by CCK-8 assays, flow cytometry, and Hoechst staining. A luciferase reporter assay was performed to determine whether Runx2 is a target gene of miR-218. Results: Our results showed that glucose up-regulated miR-218 expression, suppressed proliferation, and induced the apoptosis of ARPE-19 cells. We verified that miR-218 could inhibit the proliferation and facilitate the apoptosis of ARPE-19 cells, while inhibition of miR-218 expression produced the opposite effects. In terms of mechanism, we demonstrated that RUNX2 was a direct target of miR-218. Functional experiments showed that Runx2 served as a miR-218 target to help inhibit the proliferation and induction of apoptosis in ARPE-19 cells. Conclusion: Our findings suggest the miR-218/Runx2 axis as a potential target for treating diabetic retinopathy (DR).

Exploring the Mechanism of Action Compound‐Xueshuantong Capsule in Diabetic Retinopathy Treatment Based on Network Pharmacology

“…A large number of studies [ 34 – 37 ] have shown that the activity of transcription factors in retinal cells in high glucose environment is affected, and abnormal changes can occur in the processes of proliferation, apoptosis, oxidative stress, inflammation, and angiogenesis. To some extent, the clinical symptoms of DR can be improved by regulating the activity of transcription factors and affecting related pathways.…”

The Impact of miRNAs in Health and Disease of Retinal Pigment Epithelium

“…On the contrary, upregulation of miR-218 accelerates the apoptosis of ARPE-19 cells, negatively regulating Runx2 . These finding reveal that miR-218/ Runx2 axis could be a therapeutic target for retinal diseases ( Yao et al, 2019 ) ( Figure 4 ).…”

“…Importantly, the inhibition of miR-410 facilitated RPE differentiation in both AESCs and umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) by derepression multiple RPE development-relevant genes, such as RPE65 and OTX2 ( Choi et al, 2015 , 2017 ). Moreover, multiple studies have reported that inhibition of RPE proliferation and migration were induced by increased expression miR-451a ( Shao et al, 2019 ) and miR-218 ( Yao et al, 2019 ). On the other hand, an overproliferative effect of miR-182 ( Figure 1 ) was reported to downregulate the p-Akt pathway in RPE via repression of c-Met expression ( Wang et al, 2016a ).…”

Circ_ZFR contributes to the paclitaxel resistance and progression of non-small cell lung cancer by upregulating KPNA4 through sponging miR-195-5p

“…As a novel class of non-coding RNAs (ncRNAs), circular RNAs (circRNAs) possess covalent closed loops and function as crucial regulators in tumor carcinogenesis and chemoresistance [ 7 , 8 ]. For example, circPVT1 contributed to PTX resistance and cell invasion and repressed apoptosis in gastric cancer [ 9 ]. Circ_0035483 improved gemcitabine resistance and facilitated tumorigenesis in renal cancer through regulating miR-335/CCNB1 axis [ 10 ].…”