The long noncoding RNA myocardial infarction-associated transcript modulates the epithelial-mesenchymal transition in renal interstitial fibrosis.
AIMS
Renal interstitial fibrosis (RIF) is marked by the epithelial-mesenchymal transition (EMT) and excessive extracellular matrix deposition. The long noncoding RNA myocardial infarction-associated transcript (MIAT) facilitates RIF; however, the molecular mechanism of MIAT in RIF remains unclear. Here, we explored the possible underlying mechanisms through which MIAT modulates RIF.


MATERIALS AND METHODS
MIAT expression in human renal fibrotic tissues and unilateral ureteral obstruction (UUO) model mice was detected by qPCR. Transforming growth factor β1 (TGF-β1) was introduced to stimulate the EMT in human renal proximal tubular epithelial (HK-2) cells. CCK8, EdU, transwell and wound healing assays were employed to measure cell viability, proliferation, and migration respectively. RNA immunoprecipitation (RIP) assays and dual luciferase reporter assays were applied to determine the relationships among MIAT, miR-145, and EIF5A2.


KEY FINDINGS
MIAT was upregulated in human renal fibrotic tissues and UUO model mice compared with normal tissue adjacent to renal tumors and sham operation mice, respectively. MIAT knockdown reduced cell viability, proliferation, migration, and the EMT in HK-2 cells. Additionally, MIAT served as an endogenous sponge for miR-145 in the TGF-β1-induced-EMT in HK-2 cells, as demonstrated by dual luciferase reporter assays and RIP assays. EIF5A2 was confirmed as a target of miR-145, and MIAT knockdown suppressed EIF5A2 expression by sponging miR-145. Downregulation of EIF5A2 partly reversed induction of the EMT by miR-145 inhibitor transfection.


SIGNIFICANCE
MIAT promoted cell viability, proliferation, migration, and the EMT via regulation of the miR-145/EIF5A2 axis. These data established a potential therapy for RIF.
['Wang|Zhaohui|Z|', 'Zhang|Bo|B|', 'Chen|Zhi|Z|', 'He|Yao|Y|', 'Ru|Feng|F|', 'Liu|Peihua|P|', 'Chen|Xiang|X|']
D000818:Animals D016022:Case-Control Studies D058750:Epithelial-Mesenchymal Transition D005355:Fibrosis D005786:Gene Expression Regulation D006801:Humans D007674:Kidney Diseases D008297:Male D051379:Mice D008810:Mice, Inbred C57BL D035683:MicroRNAs D010448:Peptide Initiation Factors D062085:RNA, Long Noncoding D016601:RNA-Binding Proteins D053773:Transforming Growth Factor beta1 D014517:Ureteral Obstruction
Long noncoding RNA Myocardial infarction-associated transcript Epithelial-mesenchymal transition Renal interstitial fibrosis Eukaryotic translation initiation factor 5A2 microRNA-145