4.6 Article

MicroRNA signatures in chemotherapy resistant esophageal cancer cell lines

Journal

WORLD JOURNAL OF GASTROENTEROLOGY
Volume 20, Issue 40, Pages 14904-14912

Publisher

BAISHIDENG PUBLISHING GROUP INC
DOI: 10.3748/wjg.v20.i40.14904

Keywords

Esophageal cancer; MicroRNA; Chemotherapy; Resistance; Target

Funding

  1. German Research Foundation (DFG) [Hu 1763/1-1]
  2. National Health and Medical Research Council of Australia [595964]

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AIM: To investigate expression of microRNA (miRNA) and potential targets in chemotherapy resistant esophageal cancer cell lines. METHODS: An in-vitro model of acquired chemotherapy resistance in esophageal adeno- (EAC) and squamous cell carcinoma (ESCC) cells was used, and microRNA expression profiles for cisplatin or 5-fluorouracil (5-FU) resistant variants vs chemotherapy sensitive controls were compared using microarray and quantitative real-time polymerase chain reaction (PCR). The expression of chemotherapy-relevant genes potentially targeted by the dysregulated microRNAs in the chemotherapy resistant variants was also evaluated. RESULTS: Chemotherapy resistant sublines were found to have specific miRNA signatures, and these miRNA signatures were different for the cisplatin vs 5-FU resistant cells from the same tumor cell line, and also for EAC vs ESCC cells with resistance to the same specific chemotherapy agent. Amongst others, miR-27b-3p, miR-193b-3p, miR-192-5p, miR-378 a-3p, miR-125a-5p and miR-18a-3p were dysregulated, consistent with negative posttranscriptional control of KRAS, TYMS, ABCC3, CBL-B and ERBB2 expression via these miRNAs. CONCLUSION: The current study supports the hypothesis that microRNA expression has an impact on chemotherapy resistance in esophageal cancer. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.

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