AUTHOR=Nadda Neeti , Paul Shashi Bala , Yadav Dawesh P. , Kumar Sonu , Sreenivas Vishnubhatla , Saraya Anoop , Gamanagatti Shivanand , Acharya Subrat Kumar , Shalimar  , Nayak Baibaswata 

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

JOURNAL=Frontiers in Oncology

VOLUME=Volume 10 - 2020

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.604540

DOI=10.3389/fonc.2020.604540

ISSN=2234-943X

ABSTRACT=Background: Dysregulated oncomiRs are attributed to hepatocellular carcinoma (HCC) through targeting mTOR signaling pathway responsible for cell growth and proliferation. The potential of these oncomiRs as biomarker for tumor response or as target for therapy needs to be evaluated. 
AIM: Tumor response assessment by OncomiR changes following locoregional therapy (LRT) and targeting of these oncomiRs modulating pathway  
Methods: All consecutive viral-HCC patients of BCLC stage-A/B undergoing LRT were included. OncomiRs (miR-21, -221 and -16) change in circulation and AFP-ratio at one-month post-LRT to baseline was estimated to differentiate various categories of response as per mRECIST criteria. OncomiR modulating mTOR pathway was studied by generating miR-21 and miR-221 over-expressing Huh7 stable cell lines.  
Results: Post-LRT tumor response was assessed in 90 viral-HCC patients (CR, 40%; PR, 31%, and PD, 29%). Significant increase of miRNA -21 and-221 expression was observed in PD (p=0.040, 0.047) and PR patients (miR-21, p=0.045). Fold changes of miR-21 can differentiate response in group (CR from PR+PD) at AUROC 0.718 (95% CI, 0.572- 0.799) and CR from PR at AUROC 0.734 (95% CI, 0.595-0.873). Overexpression of miR-21 in hepatoma cell line had shown increased phosphorylation p70S6K, the downstream regulator of cell proliferation in mTOR pathway. Upregulation of AKT, mTOR and RPS6KB1 genes were found significant (P<0.005) and anti-miR-21 specifically reduced mTOR gene (P=0.02) expression.
Conclusions: The miR-21 fold change correlates well with imaging in predicting tumor response. Overexpression of miR-21 has a role in HCC through mTOR pathway activation and can be targeted.