Low MiR-10b-3p Associated with Sorafenib Resistance in Hepatocellular Carcinoma

Overview

Journal Br J Cancer

Specialty Oncology

Date 2022 Mar 3

PMID 35236936

Authors

Yu-Yun Shao

Pai-Sheng Chen

Liang-In Lin

Bin-Shyun Lee

Andrew Ling

Ann-Lii Cheng

Chiun Hsu

Da-Liang Ou

Affiliations

Soon will be listed here.

Abstract

Background: Sorafenib is one of the standard first-line therapies for advanced hepatocellular carcinoma (HCC). Unfortunately, there are currently no appropriate biomarkers to predict the clinical efficacy of sorafenib in HCC patients. MicroRNAs (miRNAs) have been studied for their biological functions and clinical applications in human cancers.

Methods: In this study, we found that miR-10b-3p expression was suppressed in sorafenib-resistant HCC cell lines through miRNA microarray analysis.

Results: Sorafenib-induced apoptosis in HCC cells was significantly enhanced by miR-10b-3p overexpression and partially abrogated by miR-10b-3p depletion. Among 45 patients who received sorafenib for advanced HCC, those with high miR-10b-3p levels, compared to those with low levels, exhibited significantly longer overall survival (OS) (median, 13.9 vs. 3.5 months, p = 0.021), suggesting that high serum miR-10b-3p level in patients treated with sorafenib for advanced HCC serves as a biomarker for predicting sorafenib efficacy. Furthermore, we confirmed that cyclin E1, a known promoter of sorafenib resistance reported by our previous study, is the downstream target for miR-10b-3p in HCC cells.

Conclusions: This study not only identified the molecular target for miR-10b-3p, but also provided evidence that circulating miR-10b-3p may be used as a biomarker for predicting sorafenib sensitivity in patients with HCC.

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