miR-133b Suppresses Invasion and Migration of Gastric Cancer Cells via the COL1A1/TGF-β Axis

Yuan Guo1, Guochun Lu1, Huahui Mao1

  • 1Department of General Surgery, First People's Hospital of Tonglu, Hangzhou 311500, People's Republic of China.

Oncotargets and Therapy
|September 5, 2020
PubMed
Abstract

Insights

MicroRNA-133b (miR-133b) inhibits gastric cancer (GC) cell invasion and migration by targeting COL1A1 and suppressing the TGF-β pathway. This finding offers new avenues for GC diagnosis and targeted therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Gastric cancer (GC) remains a significant global health challenge.
  • Understanding the molecular mechanisms underlying GC cell invasion and migration is crucial for developing effective therapies.

Purpose of the Study:

  • To elucidate the regulatory role of miR-133b in gastric cancer cell invasion and migration.
  • To investigate the involvement of the COL1A1/TGF-β signaling axis in miR-133b-mediated GC progression.

Main Methods:

  • Bioinformatic analysis of TCGA database for miRNA and gene expression profiling.
  • Quantitative real-time PCR (qRT-PCR) to assess gene expression levels.
  • Cellular assays including CCK-8, wound healing, and Transwell assays to evaluate cell proliferation, migration, and invasion.
  • Western blot analysis for epithelial-mesenchymal transition (EMT) markers.
  • Dual-luciferase reporter assays to confirm gene interactions.

Main Results:

  • miR-133b was significantly downregulated in GC tissues, while COL1A1 expression was upregulated.
  • Overexpression of miR-133b inhibited GC cell invasion, migration, and EMT, whereas silencing miR-133b had opposite effects.
  • COL1A1 was identified as a direct target gene of miR-133b.
  • COL1A1 was enriched in the TGF-β signaling pathway, and its activation promoted GC cell proliferation and migration.
  • miR-133b overexpression suppressed the TGF-β pathway, and simultaneous overexpression of miR-133b and COL1A1 reversed the inhibitory effects.

Conclusions:

  • miR-133b acts as a tumor suppressor in gastric cancer by inhibiting cell invasion and migration through the COL1A1/TGF-β axis.
  • This study provides novel insights into the molecular pathogenesis of GC.
  • The miR-133b/COL1A1/TGF-β pathway represents a potential therapeutic target for gastric cancer treatment.

Related Concept Videos

MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
3.5K
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After...
23.6K
Cancer Cell Migration through Invadopodia01:35

Cancer Cell Migration through Invadopodia

Invadosome is a broad category of cell surface structures with proteolytic activity that  degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However,...
3.0K