Bibliographic Details
| Title: |
Prognostic and Therapeutic Potentials of OncomiRs Modulating mTOR Pathways in Virus-Associated Hepatocellular Carcinoma |
| Authors: |
Neeti Nadda, Shashi Bala Paul, Dawesh P. Yadav, Sonu Kumar, Vishnubhatla Sreenivas, Anoop Saraya, Shivanand Gamanagatti, Subrat Kumar Acharya, Shalimar, Baibaswata Nayak |
| Source: |
Frontiers in Oncology, Vol 10 (2021) |
| Publisher Information: |
Frontiers Media S.A., 2021. |
| Publication Year: |
2021 |
| Collection: |
LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| Subject Terms: |
hepatocellular carcinoma, loco-regional therapy, miRNA, alpha-fetoprotein, oncomiR, hepatitis virus, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| More Details: |
BackgroundDysregulated 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.AIMTumor response assessment by OncomiR changes following locoregional therapy (LRT) and targeting of these oncomiRs modulating pathwayMethodsAll 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 1-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 overexpressing Huh7 stable cell lines.ResultsPost-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 PD 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.ConclusionsThe 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. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2234-943X |
| Relation: |
https://www.frontiersin.org/articles/10.3389/fonc.2020.604540/full; https://doaj.org/toc/2234-943X |
| DOI: |
10.3389/fonc.2020.604540 |
| Access URL: |
https://doaj.org/article/260ed1a81a1e42dbb40a52b3ac677083 |
| Accession Number: |
edsdoj.260ed1a81a1e42dbb40a52b3ac677083 |
| Database: |
Directory of Open Access Journals |
