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Downregulation of miR-33a-5p in Hepatocellular Carcinoma: A Possible Mechanism for Chemotherapy Resistance

BACKGROUND: Multi-drug resistance is one of the major problems limiting the efficacy of cisplatin (CDDP) in treatment of hepatocellular carcinoma (HCC), and abnormal microRNA (miRNA) expression in drug-resistant cell lines plays an important role in liver cancer chemotherapy resistance. MATERIAL/MET...

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Autores principales: Meng, Wei, Tai, Yan, Zhao, Hui, Fu, Binsheng, Zhang, Tong, Liu, Wei, Li, Hua, Yang, Yang, Zhang, Qi, Feng, Yuliang, Chen, Guihua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: International Scientific Literature, Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5362191/
https://www.ncbi.nlm.nih.gov/pubmed/28291769
http://dx.doi.org/10.12659/MSM.902692
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author Meng, Wei
Tai, Yan
Zhao, Hui
Fu, Binsheng
Zhang, Tong
Liu, Wei
Li, Hua
Yang, Yang
Zhang, Qi
Feng, Yuliang
Chen, Guihua
author_facet Meng, Wei
Tai, Yan
Zhao, Hui
Fu, Binsheng
Zhang, Tong
Liu, Wei
Li, Hua
Yang, Yang
Zhang, Qi
Feng, Yuliang
Chen, Guihua
author_sort Meng, Wei
collection PubMed
description BACKGROUND: Multi-drug resistance is one of the major problems limiting the efficacy of cisplatin (CDDP) in treatment of hepatocellular carcinoma (HCC), and abnormal microRNA (miRNA) expression in drug-resistant cell lines plays an important role in liver cancer chemotherapy resistance. MATERIAL/METHODS: We established stable Hep3B and 97L HCC cell strains resistant to CDDP, both in vitro and in vivo. A combination of microRNA microarray and RT-qPCR experiments were used to screen differentially expressed miRNAs in HCC cell strains. A CCK-8 assay was carried out to detect and calculate the survival rates and relative inhibitory rates. Oligonucleotide transfection was used to confirm the regulatory function of the miRNA in HCC drug resistance. RESULTS: The IC50 of Hep3B/CDDP(v), 97L/CDDP(v), Hep3B/CDDP(s), and 97L/CDDP(s) were significantly higher than that of their parental cells. Moreover, the doubling time of drug-resistant cells increased compared with their parent cells. MiRCURYTM LNA Array (v 16.0) high-throughput tests of resistant cell models and their parent cells showed that there were 5 downregulated microRNAs in the 4 drug-resistant cell lines, and we chose hsa-miR-33a-5p as our target for further study. Oligonucleotide transfection showed that miR-33a-5p overexpression increased the cisplatin sensitivity of Hep3B/CDDP(v) and 97L/CDDP(v) drug-resistant cells and reduced their resistance. Additionally, inhibition of miR-33a-5p expression reduced cisplatin sensitivity in Hep3B and 97L and increased their drug resistance. CONCLUSIONS: This study confirmed that the most downregulated microRNA, miR-33a-5p, can mediate the cisplatin resistance of HCC cells, providing a new and feasible direction for research into combatting liver cancer chemotherapy resistance.
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spelling pubmed-53621912017-03-29 Downregulation of miR-33a-5p in Hepatocellular Carcinoma: A Possible Mechanism for Chemotherapy Resistance Meng, Wei Tai, Yan Zhao, Hui Fu, Binsheng Zhang, Tong Liu, Wei Li, Hua Yang, Yang Zhang, Qi Feng, Yuliang Chen, Guihua Med Sci Monit Lab/In Vitro Research BACKGROUND: Multi-drug resistance is one of the major problems limiting the efficacy of cisplatin (CDDP) in treatment of hepatocellular carcinoma (HCC), and abnormal microRNA (miRNA) expression in drug-resistant cell lines plays an important role in liver cancer chemotherapy resistance. MATERIAL/METHODS: We established stable Hep3B and 97L HCC cell strains resistant to CDDP, both in vitro and in vivo. A combination of microRNA microarray and RT-qPCR experiments were used to screen differentially expressed miRNAs in HCC cell strains. A CCK-8 assay was carried out to detect and calculate the survival rates and relative inhibitory rates. Oligonucleotide transfection was used to confirm the regulatory function of the miRNA in HCC drug resistance. RESULTS: The IC50 of Hep3B/CDDP(v), 97L/CDDP(v), Hep3B/CDDP(s), and 97L/CDDP(s) were significantly higher than that of their parental cells. Moreover, the doubling time of drug-resistant cells increased compared with their parent cells. MiRCURYTM LNA Array (v 16.0) high-throughput tests of resistant cell models and their parent cells showed that there were 5 downregulated microRNAs in the 4 drug-resistant cell lines, and we chose hsa-miR-33a-5p as our target for further study. Oligonucleotide transfection showed that miR-33a-5p overexpression increased the cisplatin sensitivity of Hep3B/CDDP(v) and 97L/CDDP(v) drug-resistant cells and reduced their resistance. Additionally, inhibition of miR-33a-5p expression reduced cisplatin sensitivity in Hep3B and 97L and increased their drug resistance. CONCLUSIONS: This study confirmed that the most downregulated microRNA, miR-33a-5p, can mediate the cisplatin resistance of HCC cells, providing a new and feasible direction for research into combatting liver cancer chemotherapy resistance. International Scientific Literature, Inc. 2017-03-14 /pmc/articles/PMC5362191/ /pubmed/28291769 http://dx.doi.org/10.12659/MSM.902692 Text en © Med Sci Monit, 2017 This work is licensed under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
spellingShingle Lab/In Vitro Research
Meng, Wei
Tai, Yan
Zhao, Hui
Fu, Binsheng
Zhang, Tong
Liu, Wei
Li, Hua
Yang, Yang
Zhang, Qi
Feng, Yuliang
Chen, Guihua
Downregulation of miR-33a-5p in Hepatocellular Carcinoma: A Possible Mechanism for Chemotherapy Resistance
title Downregulation of miR-33a-5p in Hepatocellular Carcinoma: A Possible Mechanism for Chemotherapy Resistance
title_full Downregulation of miR-33a-5p in Hepatocellular Carcinoma: A Possible Mechanism for Chemotherapy Resistance
title_fullStr Downregulation of miR-33a-5p in Hepatocellular Carcinoma: A Possible Mechanism for Chemotherapy Resistance
title_full_unstemmed Downregulation of miR-33a-5p in Hepatocellular Carcinoma: A Possible Mechanism for Chemotherapy Resistance
title_short Downregulation of miR-33a-5p in Hepatocellular Carcinoma: A Possible Mechanism for Chemotherapy Resistance
title_sort downregulation of mir-33a-5p in hepatocellular carcinoma: a possible mechanism for chemotherapy resistance
topic Lab/In Vitro Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5362191/
https://www.ncbi.nlm.nih.gov/pubmed/28291769
http://dx.doi.org/10.12659/MSM.902692
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