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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Physiol. | doi: 10.3389/fphys.2019.01337

Upregulation of lncRNA Malat1 induced proliferation and migration of airway smooth muscle cells via miR-150-eIF4E/Akt signaling

Li Lin1, Qinghai Li1, Wanming Hao1, Yu Zhang1, Long Zhao1* and  Wei Han1*
  • 1Qingdao Municipal Hospital, Qingdao University Medical College, China

The increased proliferation and migration of airway smooth muscle cells (ASMCs) are critical processes in the formation of airway remodeling in asthma. Long non-coding RNAs (lncRNAs) have emerged as key mediators of diverse physiological and pathological processes, and are involved in the pathogenesis of various diseases, including asthma. LncRNA Malat1 has been widely reported to regulate the proliferation and migration of multiple cell types and be involved in the pathogenesis of various human diseases. However, it remains unknown whether Malat1 regulates ASMC proliferation and migration. Here, we explored the function of Malat1 in ASMC proliferation and migration in vitro stimulated by platelet-derived growth factor BB (PDGF-BB), and the underlying molecular mechanism involved. The results showed that Malat1 was significantly upregulated in ASMCs treated with PDGF-BB, and knockdown of Malat1 effectively inhibited ASMC proliferation and migration induced by PDGF-BB. Our data also showed that miR-150 was a target of Malat1 in ASMCs, and inhibited PDGF-BB-induced ASMC proliferation and migration, whereas the inhibition effect was effectively reversed by Malat1 overexpression. Additionally, translation initiation factor 4E (eIF4E), an important regulator of Akt signaling, was identified to be a target of miR-150, and both eIF4E knockdown and Akt inhibitor GSK690693 inhibited PDGF-BB-induced ASMC proliferation and migration. Collectively, these data indicate that Malat1, as a competing endogenous RNA (ceRNA) for miR-150, derepresses eIF4E expression and activates Akt signaling, thereby being involved in PDGF-BB-induced ASMC proliferation and migration. These findings suggest that Malat1 knockdown may present a new target to limit airway remodeling in asthma.

Keywords: AKT signaling, eIF4E, MiR-150, MALAT1, Asthma

Received: 07 May 2019; Accepted: 08 Oct 2019.

Copyright: © 2019 Lin, Li, Hao, Zhang, Zhao and Han. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Prof. Long Zhao, Qingdao Municipal Hospital, Qingdao University Medical College, Qingdao, 266021, Shandong Province, China, 246zhaolong@protonmail.com
Prof. Wei Han, Qingdao Municipal Hospital, Qingdao University Medical College, Qingdao, 266021, Shandong Province, China, hanwei0713qw@163.com