LncRNA MITA Improves Diabetic Mellitus Erectile Dysfunction by Regulating miR-34a-5P/KLF4 Axis

Jing Chen, Ligang Ren, Kaisen Liao, Chao Feng, Wei Shen

Article ID: 6906
Vol 36, Issue 3, 2022
DOI: https://doi.org/10.23812/j.biol.regul.homeost.agents.20223603.80
Received: 9 July 2022; Accepted: 9 July 2022; Available online: 9 July 2022; Issue release: 9 July 2022

Abstract

Background: Long non-coding RNAs (lncRNAs) are involved in various physiological and pathological processes. This study aimed to investigate the role of long non-coding RNA myocardial infarction associated transcript (lncRNA MIAT)-mediated miR-34a-5p/KLF4 axis in the phenotypic transformation of corpus cavernosum smooth muscle cells (CCSMCs) in diabetes mellitus erectile dysfunction (DMED) rats. Methods: We constructed a DMED rat model and observed the pathological changes and apoptosis of cavernous tissues using HE/Masson and TUNEL staining. The expressions of lncRNA MIAT, miR-34a-5p, and KLF4 in cavernous tissues were detected by qRT-PCR or immunohistochemistry. Immunohistochemistry assay was used to identify the isolated CCSMCs, and cell vitality and migration were examined using CCK-8 and wound healing. The binding of miR-34a-5p and KLF4 was determined by a dual-luciferase report assay. Oxidative stress levels were detected by ELISA. The expressions of lncRNA MIAT, miR-34a-5p, KLF4, α-SMA, SM-MHC, and OPN were detected by immunofluorescence, qRT-PCR or western blot. Results: LncRNA MIAT and KLF4 were up-regulated in the cavernous tissues of DMED rats. MiR-34a-5p mimic decreased KLF4-3′UTR-WT luciferase activity. High glucose (HG) induction promoted the proliferation and migration of CCSMCs. LncRNA MIAT and KLF4 silencing inhibited the proliferation, migration, surface transformation and oxidative stress of HG-CCSMCs compared to miR-34a-5p inhibition. KLF4 silencing neutralized the positive effect by miR-34-5p inhibition. Conclusions: LncRNA MIAT facilitates phenotypic transformation and oxidative stress of CCSMCs in DMED rats via mediating the miR-34a-5p/KLF4 axis.


Keywords

long non-coding RNA MIAT;microRNA-34a-5P;Krüppel-like factor 4;diabetes mellitus erectile dysfunction


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