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

Bioengineered. 2022 Mar;13(3):6978-6995. doi: 10.1080/21655979.2022.2037921.

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.

Keywords: Smad7; TGF-β/EMT pathways; gastric cancer; lncRNA MBNL1-AS1; miR-424-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Humans
  • MicroRNAs* / genetics
  • RNA, Long Noncoding* / genetics
  • RNA-Binding Proteins / genetics
  • Smad7 Protein / genetics
  • Stomach Neoplasms* / genetics
  • Transforming Growth Factor beta / genetics

Substances

  • MBNL1 protein, human
  • MIRN424 microrna, human
  • MicroRNAs
  • RNA, Long Noncoding
  • RNA-Binding Proteins
  • SMAD7 protein, human
  • Smad7 Protein
  • Transforming Growth Factor beta

Grants and funding

This research was supported by Zhejiang Provincial Natural Science Foundation of China under Grant No.LQ21H160012.