lncRNA MIAT increases cell viability, migration, EMT and ECM production in age‑related cataracts by regulating the miR‑181a/CTGF/ERK signaling pathway

Abstract

Age-related cataract (ARC) is a common cause of blindness in elderly individuals. Long non-coding RNA (lncRNA) myocardial infarction associated transcript (MIAT) has been reported to participate in various biological processes in a number of diseases; however, the biological mechanism underlying MIAT during ARC is not completely understood. The expression levels of MIAT, microRNA (miR)-181a and connective tissue growth factor (CTGF) were measured by reverse transcription-quantitative PCR. The protein expression levels of CTGF, α-smooth muscle actin, fibronectin, collagen type I, ERK, phosphorylated (p)-ERK, mitogen-activated protein kinase (MEK), and p-MEK were detected by western blotting. Cell viability and migration were assessed using MTT and Transwell assays, respectively. Moreover, a dual-luciferase reporter assay was performed to investigate the interaction between miR-181a and MIAT or CTGF. MIAT and CTGF were upregulated, while miR-181a was significantly downregulated in ARC tissues compared with normal tissues. MIAT or CTGF knockdown decreased cell viability, migration, epithelial-mesenchymal transition and extracellular matrix production in TGF-β2-treated SRA01/04 cells. It was hypothesized that miR-181a may be sponged by MIAT and may target CTGF. Furthermore, the miR-181a inhibitor reversed the inhibitory effect of MIAT knockdown on the progression of TGF-β2-treated SRA01/04 cells. Moreover, CTGF knockdown also reversed MIAT overexpression-mediated progression of TGF-β2-treated SRA01/04 cells. In addition, MIAT and CTGF regulated the activity of the ERK signaling pathway. The results suggested that MIAT may regulate the progression of ARC via the miR-181a/CTGF/ERK signaling pathway, which may serve as a novel therapeutic target for ARC.

Expression and function of CCN2-derived circRNAs in chondrocytes

“…These results suggest that CCN2 -derived circRNA (A) has a function in the regulation of ACAN mRNA expression specifically. Of note, this circRNA contains a miR-181-5p target in its 3′-UTR segment (Ling et al 2020 ), and our previous study clearly showed that exogenous miR-181a-5p drastically decreased the ACAN mRNA in HCS-2/8 cells, strongly suggesting their direct interaction (Sumiyoshi et al 2013 ). Therefore, to investigate the suppression mechanism of ACAN mRNA expression by knockdown of CCN2 -derived circRNA (A), a reporter gene assay was performed using a firefly luciferase reporter that contains a target sequence of miR-181-5p (Sumiyoshi et al 2013 ).…”

lncRNA: a promising target for cataracts

“…To explore lncRNAs in the physiopathological mechanism of cataracts, Shen et al compared the lens of cataract patients to that of normal people and found that lncRNA MIAT is a speci c biomarker of cataract, and lncRNA MIAT participates in regulating the function of HLECs through miR-150-5p/Akt, which has an impact on cell viability, cell proliferation, and apoptosis [51] . Studies have also shown that MIAT increased cell viability, migration, epithelial-mesenchymal transition (EMT), and extracellular matrix production during ARC by activating the extracellular signal-regulated kinase signaling pathway via the miR-181a/connective tissue growth factor axis [52] . Therefore, the novel regulatory network identi ed in this study may serve as a therapeutic target for ARC and provide a theoretical basis for the mechanism underlying ARC development [52] .…”

“…Studies have also shown that MIAT increased cell viability, migration, epithelial-mesenchymal transition (EMT), and extracellular matrix production during ARC by activating the extracellular signal-regulated kinase signaling pathway via the miR-181a/connective tissue growth factor axis [52] . Therefore, the novel regulatory network identi ed in this study may serve as a therapeutic target for ARC and provide a theoretical basis for the mechanism underlying ARC development [52] .…”

The Role of N6-Methyladenosine Modified Circular RNA in Pathophysiological Processes

“…Age-related cataract (ARC) is the leading cause of world blindness, which causes ~50% blindness worldwide 148 . Few circRNA has been identified in cataract.…”