LncRNA MBNL1-AS1 represses gastric cancer progression via the TGF-β pathway by modulating miR-424-5p/Smad7 axis

Abstract

Studies over the past decades have implicated lncRNAs in promoting the development, migration and invasion of gastric cancer (GC). However, the role and mechanism of lncRNA MBNL1-AS1 in GC promotion are poorly understood. In this research, qRT-PCR showed that MBNL1-AS1 was down-regulated in GC tissues and cells. Cell experiments and the animal study demonstrated that MBNL1-AS1 knockdown accelerated GC cell proliferation, migration, and invasion, thus restraining cell apoptosis. Meanwhile, overexpression of MBNL1-AS1 repressed GC cell promotion. Bioinformatics analysis confirmed that MBNL1-AS1 binds to miR-424-5p via negative modulation. Rescue experiments showed that decreased miR-424-5p level inhibited GC cell promotion by silencing MBNL1-AS1. Furthermore, Smad7 was identified as a target of miR-424-5p that could reverse the promotion of GC cell growth mediated by miR-424-5p. Western blot results proved that MBNL1-AS1 affected TGF-β/SMAD pathways by regulating the miR-424-5p/Smad7 axis. Collectively, MBNL1-AS1 restrained GC growth via the miR-424-5p/Smad7 axis and thus could be a promising target for GC therapy. These findings illustrate that lncRNA MBNL1-AS1, as a tumor suppressor gene, participates in GC progression by regulating miR-424-5p/Smad7 axis, thus activating TGF-β/EMT pathways. The evidence may provide a potential marker for GC patients.

Long noncoding RNA TMEM147-AS1 serves as a microRNA-326 sponge to aggravate the malignancy of gastric cancer by upregulating SMAD5

“…For example, CRART16 [18], LINC01270 [19] and HOXA10-AS [20] show high expression in GC and exert tumorigenic effects. In contrast, downregulation of CRYM-AS1 [21], MBNL1-AS1 [22], and HOXD-AS2 [23] have been demonstrated in GC and are capable of inhibiting cancer progression. However, little is known regarding the role of TMEM147-AS1 in GC.…”

Analysis of Long Noncoding RNAs-Related Regulatory Mechanisms in Duchenne Muscular Dystrophy Using a Disease-Related lncRNA-mRNA Pathway Network

“…GAS5 reportedly promotes wound healing by activating the HIF1A/ VEGF pathway [43]. Dysregulation of the lncRNAs MBNL1-AS1, CCDC18-AS1, LINC01290, MIR29B2CHG, and PSMB8-AS1 has been observed in many cancers [44][45][46][47][48]. NF-κB signaling is activated during DMD pathogenesis and leads to infammation and muscle degeneration [49].…”

Roles of TGF‑β signalling pathway‑related lncRNAs in cancer (Review)

“…Sakai et al ( 76 ) identified the EMT-associated lncRNA ELIT1, which enhances SMAD promoter activity via TGF-β induction and recruiting SMAD3 to the promoter region of its target gene. In addition, lncRNA MBNL2-AS1 forms a ceRNA network with miR-424-5p and SMAD7, inactivating the TGF-β/EMT pathway and inhibiting GC cell proliferation, migration and invasion ( 77 ).…”

“…lncRNAs regulate gene expression at genomic, transcriptomic and posttranscriptional levels and are recognized as biomarkers and therapeutic targets for GC ( Fig. 2 ) ( 77 , 78 ). The TGF-β signalling pathway is an important pathway that promotes development of GC and studying the effect of the interaction of this pathway with lncRNAs in the development of GC may provide an important target for early diagnosis ( 71 ).…”