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NF-κB downstream miR-1262 disturbs colon cancer cell malignant behaviors by targeting FGFR1

Weilin Zhang1,2,3, Zhongcheng Huang3, Zhigang Xiao3

  • 1The Second School of Clinical Medicine, Southern Medical University, Guangzhou 510080, China.

Acta Biochimica Et Biophysica Sinica
|October 23, 2023
PubMed

Insights

MicroRNA-1262 (miR-1262) acts as a tumor suppressor in colon cancer by targeting fibroblast growth factor receptor 1 (FGFR1). Nuclear factor kappa B (NF-κB) inhibits miR-1262, impacting cancer progression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Colorectal cancer is a leading cause of cancer-related death despite treatment advances.
  • Nuclear factor kappa B (NF-κB) signaling drives malignant transformation in inflammatory bowel diseases.
  • MicroRNAs (miRNAs) are implicated in colon cancer development and progression.

Purpose of the Study:

  • To investigate the role of deregulated miRNAs in colon cancer.
  • To identify specific functions of miRNAs in vitro and in vivo.
  • To analyze miRNA downstream targets and their regulatory mechanisms.

Main Methods:

  • Analysis of deregulated miRNAs in colon cancer tissues and cell lines.
  • In vitro functional assays using cancer cells.
  • In vivo studies using subcutaneous xenograft and lung metastasis mouse models.
  • Verification of miRNA-target binding and regulation.
  • Investigation of NF-κB binding to the miR-1262 promoter.

Main Results:

  • miR-1262 was found to be downregulated in colon cancer.
  • Overexpression of miR-1262 suppressed colon cancer cell proliferation, invasion, migration, tumor development, and metastasis.
  • miR-1262 directly targets and inhibits fibroblast growth factor receptor 1 (FGFR1).
  • FGFR1 overexpression promoted oncogenic functions, partially reversing miR-1262's effects.
  • NF-κB binds to the miR-1262 promoter, inhibiting its transcription.
  • NF-κB inhibition by CAPE showed antitumor effects, partially reversed by miR-1262 inhibition.

Conclusions:

  • miR-1262 functions as an antitumor miRNA in colon cancer by targeting FGFR1.
  • The NF-κB/miR-1262/FGFR1 axis is a key regulator of colon cancer cell phenotypes.
  • This axis influences cancer cell proliferation, invasion, and migration, offering potential therapeutic targets.
Keywords:
NF-κBcolorectal cancerfibroblast growth factor receptor 1 (FGFR1)miR-1262

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