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Targeting FHL2-E-cadherin axis by miR-340-5p attenuates colon cancer cell migration and invasion

Anwar Algaber1, Raed Madhi1,2, Avin Hawez1

  • 1Department of Clinical Sciences, Malmö, Section for Surgery, Lund University, 214 28 Malmö, Sweden.

Oncology Letters
|July 23, 2021
PubMed

Insights

MicroRNA-340-5p targets four and a half LIM domain 2 protein (FHL2) to reduce colon cancer cell migration and invasion. This study suggests miR-340-5p can antagonize colon cancer metastasis by regulating the FHL2-E-cadherin axis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Four and a half LIM domain 2 protein (FHL2) is implicated in cancer metastasis.
  • MicroRNA (miR)-340-5p is known to regulate cancer cell migration.
  • The interplay between miR-340-5p and FHL2 in colon cancer metastasis requires further investigation.

Purpose of the Study:

  • To investigate whether miR-340-5p can attenuate colon cancer cell migration and invasion by targeting FHL2 expression.
  • To elucidate the molecular mechanism underlying the regulation of FHL2 by miR-340-5p in colon cancer cells.

Main Methods:

  • Analysis of FHL2 expression in colon cancer microarray datasets and cell lines (HT-29, AZ-97) using Qlucore omics explorer and RT-qPCR.
  • Evaluation of colon cancer cell migration and invasion following transfection with miR-340-5p mimic, control, or target site blocker.
  • Assessment of FHL2 and E-cadherin (E-cad) protein and mRNA expression via confocal microscopy and RT-qPCR.
  • Bioinformatics analysis to identify potential binding sites of miR-340-5p on FHL2 mRNA.

Main Results:

  • FHL2 expression was found to be lower in primary colon cancer tissues compared to normal colonic mucosa.
  • A significant inverse correlation between miR-340-5p and FHL2 expression was observed in colon cancer cell lines.
  • Transfection with miR-340-5p mimic decreased FHL2 expression, suppressed colon cancer cell migration and invasion, and reversed E-cadherin disruption.
  • Bioinformatics analysis confirmed a putative binding site for miR-340-5p on FHL2 mRNA, and blocking this site abrogated the observed effects.

Conclusions:

  • miR-340-5p antagonizes colon cancer cell metastasis by targeting FHL2.
  • The FHL2-E-cadherin axis is a key pathway regulated by miR-340-5p in colon cancer.
  • These findings highlight the potential of miR-340-5p as a therapeutic agent for colon cancer metastasis.
Keywords:
cell migrationcolon cancerfour and a half LIM domains protein 2metastasismicroRNAs

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