Prognostic and Therapeutic Potentials of OncomiRs Modulating mTOR Pathways in Virus-Associated Hepatocellular

Neeti Nadda1, Shashi Bala Paul2, Dawesh P Yadav1

  • 1Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India.

Frontiers in Oncology
|February 22, 2021
PubMed
Abstract

Insights

MicroRNA-21 (miR-21) levels can predict hepatocellular carcinoma (HCC) treatment response. Targeting miR-21 may offer a new therapeutic strategy for HCC by modulating the mTOR pathway.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Dysregulated oncomiRs (oncogenic microRNAs) contribute to hepatocellular carcinoma (HCC) by targeting the mTOR signaling pathway, which controls cell growth and proliferation.
  • Evaluating oncomiRs as biomarkers for tumor response and as therapeutic targets is crucial for HCC management.

Purpose of the Study:

  • To assess tumor response to locoregional therapy (LRT) in HCC patients based on changes in circulating oncomiRs (miR-21, -221, -16) and AFP-ratio.
  • To investigate the role of oncomiRs in modulating the mTOR pathway through experimental models.

Main Methods:

  • Analysis of consecutive viral-HCC patients (BCLC stage A/B) undergoing LRT.
  • Measurement of oncomiR (miR-21, -221, -16) and AFP-ratio changes at 1-month post-LRT compared to baseline.
  • Generation of miR-21 and miR-221 overexpressing Huh7 cell lines to study mTOR pathway modulation.

Main Results:

  • Tumor response to LRT in 90 patients: 40% complete response (CR), 31% partial response (PR), 29% progressive disease (PD).
  • Significant increase in miR-21 and miR-221 expression observed in PD and PR groups post-LRT (p < 0.05).
  • miR-21 fold change demonstrated predictive value for response (AUROC 0.718-0.734). Overexpression of miR-21 activated mTOR pathway components (AKT, mTOR, RPS6KB1), while anti-miR-21 reduced mTOR expression.

Conclusions:

  • Circulating miR-21 fold change is a reliable predictor of HCC treatment response, correlating with imaging-based assessments.
  • miR-21 plays a role in HCC progression via mTOR pathway activation and represents a potential therapeutic target.

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