Low miR-10b-3p associated with sorafenib resistance in hepatocellular carcinoma

Yu Yun Shao, Pai Sheng Chen, Liang In Lin, Bin Shyun Lee, Andrew Ling, Ann Lii Cheng, Chiun Hsu, Da Liang Ou

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1806-1814
Number of pages9
JournalBritish Journal of Cancer
Volume126
Issue number12
DOIs
Publication statusAccepted/In press - 2022

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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