TY - JOUR
T1 - Low miR-10b-3p associated with sorafenib resistance in hepatocellular carcinoma
AU - Shao, Yu Yun
AU - Chen, Pai Sheng
AU - Lin, Liang In
AU - Lee, Bin Shyun
AU - Ling, Andrew
AU - Cheng, Ann Lii
AU - Hsu, Chiun
AU - Ou, Da Liang
N1 - Funding Information:
This study was supported by the following research grants: NTU-109L901403, NTU- 110L901404 (from Ministry of Education, Taiwan), MOST 106-2314-B-002-229-MY3, MOST 107-3017-F-002-002, MOST 107-2314-B-002-210-MY3, MOST 108-2314-B-002-075-MY3, MOST 108-3017-F-002-004, MOST 109-2634-F-002-043, 109-2314-B-002 -229 -MY3, MOST 110-2634-F-002-044 (from Ministry of Science and Technology, Taiwan), YongLin Chair Grant S-01, (from National Taiwan University), UN108-010, UN109-051 (from National Taiwan University Hospital).
Funding Information:
A-LC is a consultant for and a member of the speaker’s bureau of Bayer-Schering Pharma. A-LC is a consultant of Novartis, Merck Serono, Eisai, Merck Sharp & Dohme (MSD) Corp., ONXEO, Bayer HealthCare Pharmaceuticals Inc., Bristol-Myers Squibb (BMS) Company, and Ono Pharmaceutical Co., Ltd. A-LC is an Associate Editor of Liver Cancer. CH received research grants from BMS/ONO, Roche, and Ipsen and received honorarium from the following pharmaceutical companies: AstraZeneca, Bayer, BMS/ONO, Eisai, Eli Lilly, Ipsen, Merck Serono, MSD, Novartis, Roche, TTY Biopharm.
Funding Information:
This work was financially supported by the Cancer Biology Research Group, Center of Precision Medicine, National Taiwan University, Taipei, Taiwan. The authors thank the National Center for High-performance Computing for computer time and facilities as well as the second Core Lab, Department of Medical Research, National Taiwan University Hospital for providing laboratory facilities. D-LO was supported by National Taiwan University YongLin Institute of Health Scholar.
Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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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U2 - 10.1038/s41416-022-01759-w
DO - 10.1038/s41416-022-01759-w
M3 - Article
C2 - 35236936
AN - SCOPUS:85125447508
SN - 0007-0920
VL - 126
SP - 1806
EP - 1814
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 12
ER -
