Long noncoding RNA MAGI1‐IT1 regulates cardiac hypertrophy by modulating miR‐302e/DKK1/Wnt/beta‐catenin signaling pathway

Abstract

Cardiac hypertrophy (CH) is an adaptive cardiac response to overload whose decompensation eventually leads to heart failure or sudden death. Recently, accumulating studies have indicated the implication of long noncoding RNAs (lncRNAs) in CH progression. MAGI1-IT1 is a newly-identified lncRNA that is highly associated with CH, while its specific role in CH progression remains masked. In this study, we uncovered that MAGI1-IT1 was distinctly downregulated in angiotensin (Ang) Ⅱ-induced hypertrophic H9c2 cells. Also, MAGI1-IT1 overexpression in Ang Ⅱtreated H9c2 cells strikingly abolished the enlarged surface area and the enhanced levels of hypertrophic markers such as ANP, BNP, and β-MHC. Mechanically, we found MAGI1-IT1 sponged miR-302e which was identified as a hypertrophyfacilitator here, and that miR-302e upregulation countervailed the inhibition of MAGI1-IT1 overexpression on hypertrophic cells. Moreover, it was confirmed that MAGI1-IT1 boosted DKK1 expression by absorbing miR-302e. Subsequently, we also illustrated that MAGI1-IT1 inactivated Wnt/beta-catenin signaling through a DKK1dependent pathway. Finally, both the DKK1 inhibition and LiCI (Wnt activator) supplement abrogated the hypertrophy-suppressive impact of MAGI1-IT1 on Ang Ⅱsimulated hypertrophic H9c2 cells. Jointly, our findings disclosed that MAGI1-IT1 functioned as a negative regulator in CH through inactivating Wnt/beta-catenin pathway via targeting miR-302e/DKK1 axis, revealing a novel road for CH treatment. K E Y W O R D S cardiac hypertrophy, DKK1, MAGI1-IT1, miR-302e, Wnt signaling

LncRNA SNHG1 exerts a protective role in cardiomyocytes hypertrophy via targeting miR‐15a‐5p/HMGA1 axis

“…lncRNA CHAR overexpression mitigates the repression of PTEN and activation of AKT by miR‐20b, and as such, it abrogated the deleterious effects of miR‐20b on cardiac hypertrophy (Zhang et al, 2019). lncRNA MAGI1‐IT1 functions as a negative regulator in cardiac hypertrophy by inactivating the Wnt/β‐catenin pathway via targeting miR‐302e/DKK1 axis (Zhang et al, 2020). Enforced expression of lncRNA CHRF accelerates cardiac hypertrophy in vivo and in vitro via sponging miR‐489 (Wang et al, 2014).…”

Long Non-Coding RNAs in Atrial Fibrillation: Pluripotent Stem Cell-Derived Cardiomyocytes as a Model System

“…MIAT was also found to regulate the miR-93/TLR4 axis, where sponging of miR-93 by MIAT induces TLR4 expression and hypertrophic PI3K/Akt/mTOR signaling, leading to AngII-induced hypertrophy [ 65 ]. A group of other lncRNAs that regulate miRNAs in hypertrophy are H19 [ 66 ], lncRNA-ROR [ 67 ], HOTAIR [ 68 ], DSCAM-AS1 [ 69 ], Plscr4 [ 70 ], XIST [ 71 , 72 ], SYNE1-AS1 [ 73 ], MAGI1-IT1 [ 74 ].…”

Expedition to the missing link: Long noncoding RNAs in cardiovascular diseases

“…Other examples of lncRNAs that regulate cardiac hypertrophy-related miRNA as ceRNAs include H19 [39], HOTAIR [40], lncRNA-ROR [41], MAGI1-IT1 [42], Meg3 [43], Plscr4 [44], SYNE1-AS1 [45], and XIST [46,47]. Table 1 summarizes lncRNAs that are implicated in the pathogenesis of cardiac hypertrophy and heart failure.…”