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Identification and modulation of a PI3K/AKT/mTOR pathway-targeting microRNA in order to increase colorectal cancer

Seyedeh Nasibeh Mousavikia1,2, Maryam M Matin3,4, Mohammad Taghi Bahreyni Tossi2

  • 1Department of Medical Physics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

BMC Cancer
|July 14, 2025
PubMed
Abstract

Insights

MicroRNA-16-5p enhances colorectal cancer (CRC) radiosensitivity by targeting the PI3K/AKT/mTOR pathway. This miRNA-based therapy offers a potential strategy to improve CRC treatment outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Colorectal cancer (CRC) progression is linked to the PI3K/AKT/mTOR signaling pathway.
  • MicroRNAs (miRNAs) are emerging as critical regulators of gene expression with therapeutic potential.
  • Identifying specific miRNAs can offer novel strategies to overcome radioresistance in CRC.

Purpose of the Study:

  • To identify a miRNA that enhances radiosensitivity in colorectal cancer.
  • To investigate the role of this miRNA in targeting the PI3K/AKT/mTOR signaling pathway.
  • To evaluate the therapeutic potential of miRNA-based interventions for CRC.

Main Methods:

  • Analysis of gene expression datasets from 87 CRC patients.
  • Identification of PI3K/AKT/mTOR pathway genes using KEGG database.
  • Determination of miRNA-mRNA binding sites using multiple databases (TarBase, miRTarBase, mirDIP, miRNet).
  • Transfection of selected miRNA (miR-16-5p) into CRC cell lines (LoVo, HT-29).
  • Assessment of radiosensitivity via clonogenic assays and apoptosis analysis.
  • Gene expression analysis using real-time PCR.

Main Results:

  • miR-16-5p was identified as a key miRNA involved in CRC radiosensitivity.
  • Irradiation significantly suppressed miR-16-5p expression in CRC cell lines.
  • miR-16-5p effectively suppressed target genes (CCNE1, CCND1, MYC, CDK4, HSP90AB1, PIK3CA) within the PI3K/AKT/mTOR pathway.
  • Combined transfection and irradiation decreased cell survival and increased apoptosis.

Conclusions:

  • The PI3K/AKT/mTOR pathway is implicated in colorectal cancer radioresistance.
  • miR-16-5p acts as a radiosensitizer by repressing key pathway genes.
  • miRNA-based gene therapy presents a promising approach to enhance CRC treatment efficacy and patient outcomes.
Keywords:
Colorectal CancerHsa-miR-16-5pMicroRNAPI3K/AKT/mTOR pathwayRadioresistance

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