Upregulation of LncRNA Malat1 Induced Proliferation and Migration of Airway Smooth Muscle Cells via miR-150-eIF4E/Akt Signaling

Abstract

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.

Long non-coding RNA MALAT1 exacerbates acute respiratory distress syndrome by upregulating ICAM-1 expression via microRNA-150-5p downregulation

“…By functioning as a sponge or as a competing endogenous noncoding RNA for miR-150-5p, lncRNA FOXD3-AS1 promotes hyperoxia-induced lung epithelial cell death [32]. In accordance with the findings from the current study, miR-150 has been demonstrated to be a target of MALAT1 in airway smooth muscle cells and MALAT1 can augment the expression of eIF4E, a target of miR-150, as a ceRNA for miR-150 [33].…”

A non-coding RNA network involved in KSHV tumorigenesis

“…It has been shown to regulate EGFR expression promoting carcinogenesis [Zhang et al, 2019]; it has been shown to regulate endothelial cell function and vessel growth [Michalik et al, 2014]; it has been defined as a hypoxia-induced lncRNA [Kölling et al, 2018]; it modulates ZEB1 and ZEB2 by sponging miRNAs [Xiao et al, 2015; Chen et al, 2017]. Remarkably, MALAT1 expression is induced by the platelet-derived growth factor BB (PDGF-BB) [Lin et al, 2019]. In a recent study, we have shown that the KSHV-ligand mediated activation of the PDGF signaling pathway is critical for KS development [Cavallin et al, 2018].…”

Six-ingredient-Xiao-qing-long decoction inhibited TGF-β1-induced proliferation and migration of human airway smooth muscle cells by regulating FKBP51/AKT signaling

“…AKT also known as protein kinase B, is activated by various stimuli, growth factors and hormones (Risso et al 2015;Song et al 2019). It has been reported that Akt plays a crucial role in cell survival and development (Li et al 2020), and the activation of AKT is involved in regulating the proliferation and migration of hASMC (Deng et al 2017;Lin et al 2019). A previous study demonstrated that AKT activation was significantly increased in hASMC induced by TGF-β1, while inhibition of the AKT signaling pathway significantly decreases hASMC migration (Lv et al 2019).…”