Published online Oct 28, 2014. doi: 10.3748/wjg.v20.i40.14904
Revised: May 19, 2014
Accepted: June 26, 2014
Published online: October 28, 2014
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.
Core tip: The current study demonstrates that chemotherapy resistant esophageal adeno- and squamous cell carcinoma cells present distinct microRNA (miRNA) signatures, with a number of well known resistance relevant miRNAs differentially expressed in the derived cisplatin or 5-fluorouracil resistant cell lines. Furthermore, a number of putative target genes that are known to have an impact on chemotherapy resistance are dysregulated in the chemotherapy resistant cell lines in a direction consistent with negative posttranscriptional control of target gene expression via the respective miRNA, thereby implicating a potential mediatory effect in terms of chemotherapy resistance development.