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Long noncoding RNA MAGI1‐IT1 regulates cardiac hypertrophy by modulating miR‐302e/DKK1/Wnt/beta‐catenin signaling pathway
Author(s) -
Zhang Qinghua,
Wang Fengshuang,
Wang Fenghua,
Wu Naishi
Publication year - 2020
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.28964
Subject(s) - wnt signaling pathway , dkk1 , downregulation and upregulation , beta catenin , cancer research , medicine , biology , chemistry , microbiology and biotechnology , signal transduction , gene , genetics
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 II‐treated 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 hypertrophy‐facilitator 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 DKK1‐dependent pathway. Finally, both the DKK1 inhibition and LiCI (Wnt activator) supplement abrogated the hypertrophy‐suppressive impact of MAGI1‐IT1 on Ang II‐simulated 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.