Chemotherapy-induced modification of microRNA expression in esophageal cancer

TY - JOUR

T1 - Chemotherapy-induced modification of microRNA expression in esophageal cancer

AU - Hummel, Richard

AU - Wang, Tingting

AU - Watson, David I

AU - Michael, Michael Z

AU - Van der Hoek, Mark

AU - Haier, Joerg

AU - Hussey, Damian J

PY - 2011/10

Y1 - 2011/10

N2 - Neoadjuvant chemotherapy is often used in the treatment of advanced esophageal cancer. In this study, we determined the impact of chemotherapy on microRNA (miRNA) expression in esophageal cancer cells, and whether identified changes might have biological relevance. Two esophageal carcinoma cell lines (one adenocarcinoma and one squamous cell carcinoma) were treated with cisplatin or 5-fluorouracil for 24 or 72 h. RNA was extracted from cells following 24-h treatment, and used for microarray studies. Promising miRNA candidates were selected for RT-PCR validation. Target prediction using TargetScan, combined with bioinformatic analysis (Ingenuity Pathway Analysis, IPA), was performed to evaluate the implications of the altered miRNA expression. Thirteen miRNAs (miR-199a-5p, miR-302f, miR-320a, miR-342-3p, miR-425, miR-455-3p, miR-486-3p, miR-519c-5p, miR-548d-5p, miR-617, miR-758, miR-766, miR-1286) were deregulated after 24- and/or 72-h treatment in both cell lines, and most miRNAs presented similar expression changes after short- or long-term exposure. IPA revealed that the major networks which incorporate the predicted targets, include functions such as 'Cell death', 'Cell cycle', 'Cellular growth and proliferation', 'DNA replication, recombination, and repair' and 'Drug metabolism'. Cisplatin or 5-fluorouracil alter miRNA expression in esophageal cancer cells. IPA suggests that these miRNAs may target molecular pathways involved in cell survival after chemotherapy.

AB - Neoadjuvant chemotherapy is often used in the treatment of advanced esophageal cancer. In this study, we determined the impact of chemotherapy on microRNA (miRNA) expression in esophageal cancer cells, and whether identified changes might have biological relevance. Two esophageal carcinoma cell lines (one adenocarcinoma and one squamous cell carcinoma) were treated with cisplatin or 5-fluorouracil for 24 or 72 h. RNA was extracted from cells following 24-h treatment, and used for microarray studies. Promising miRNA candidates were selected for RT-PCR validation. Target prediction using TargetScan, combined with bioinformatic analysis (Ingenuity Pathway Analysis, IPA), was performed to evaluate the implications of the altered miRNA expression. Thirteen miRNAs (miR-199a-5p, miR-302f, miR-320a, miR-342-3p, miR-425, miR-455-3p, miR-486-3p, miR-519c-5p, miR-548d-5p, miR-617, miR-758, miR-766, miR-1286) were deregulated after 24- and/or 72-h treatment in both cell lines, and most miRNAs presented similar expression changes after short- or long-term exposure. IPA revealed that the major networks which incorporate the predicted targets, include functions such as 'Cell death', 'Cell cycle', 'Cellular growth and proliferation', 'DNA replication, recombination, and repair' and 'Drug metabolism'. Cisplatin or 5-fluorouracil alter miRNA expression in esophageal cancer cells. IPA suggests that these miRNAs may target molecular pathways involved in cell survival after chemotherapy.

KW - Antineoplastic Agents

KW - Carcinoma, Squamous Cell

KW - Cell Line, Tumor

KW - Cisplatin

KW - Esophageal Neoplasms

KW - Fluorouracil

KW - Gene Expression Regulation, Neoplastic

KW - Humans

KW - MicroRNAs

KW - Prognosis

KW - RNA, Messenger

U2 - 10.3892/or.2011.1381

DO - 10.3892/or.2011.1381

M3 - SCORING: Journal article

C2 - 21743970

VL - 26

SP - 1011

EP - 1017

JO - ONCOL REP

JF - ONCOL REP

SN - 1021-335X

IS - 4

ER -