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Effect of modification of MTDH gene expression on colorectal cancer aggressiveness

Nahla E El-Ashmawy1, Enas A El-Zamarany2, Eman G Khedr1

  • 1Department of Biochemistry, Faculty of Pharmacy, Tanta University, Tanta, Egypt.

Gene
|March 6, 2019
PubMed
Abstract

Insights

Metadherin (MTDH) drives colorectal cancer (CRC) progression. Inhibiting MTDH may reduce CRC cell malignancy and affect NF-κB pathways.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Metadherin (MTDH) is an oncogene overexpressed in many cancers, including colorectal cancer (CRC).
  • Limited research exists on MTDH's role in CRC's biological behavior.
  • This study investigates MTDH's impact on CRC cell behavior through gene expression modification.

Purpose of the Study:

  • To examine the in vitro effects of altering Metadherin (MTDH) gene expression on colorectal cancer (CRC) cell behavior.
  • To assess the impact of MTDH knockdown and overexpression on key cancer-related pathways and cellular functions in CRC cells.

Main Methods:

  • Quantitative Polymerase Chain Reaction (qPCR) was used to analyze MTDH expression in Caco-2 and HCT116 CRC cell lines.
  • MTDH was downregulated in HCT116 cells using siRNA-mediated knockdown.
  • MTDH was upregulated in Caco-2 cells via plasmid transfection.

Main Results:

  • MTDH knockdown decreased multidrug resistance gene (MDR1), Snail, and NF-κB p65 expression, while increasing E-cadherin.
  • MTDH knockdown reduced anaerobic glycolysis, cell proliferation, and cancer stem cell transformation.
  • MTDH upregulation enhanced MDR1, Snail, and NF-κB p65 expression, decreased E-cadherin, and promoted proliferation, glycolysis, and stem cell traits.

Conclusions:

  • MTDH significantly promotes colorectal cancer (CRC) progression.
  • Inhibiting MTDH expression can potentially attenuate the carcinogenic behavior of CRC cells.
  • MTDH-associated NF-κB p65 signaling pathways are likely involved in mediating CRC's biological behavior.
Keywords:
Colorectal cancer stem cellsE-cadherinMDR1MTDHNF-ĸB p65Snail

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