Abstract
BackgroundChemotherapy is an important therapeutic approach for non-small cell lung cancer (NSCLC). However, a successful long-term treatment can be prevented by the occurring of chemotherapy resistance frequently, and the molecular mechanisms of chemotherapy resistance in NSCLC remain unclear. In this study, abnormal expressions of miR-17 and miR-92 families are observed in cisplatin-resistant cells, suggesting that miR-17 and miR-92 families are involved in the regulation of cisplatin resistance in NSCLC.MethodsmiRNA microarray shows that miR-17 and miR-92 families are all down-regulated in cisplatin-resistant A549/DDP cells compared with cisplatin-sensitive A549 cells. The aim of this study is to investigate the regulatory functions of miR-17 and miR-92 families on the formation of cisplatin resistance and the predictive functions of them as biomarkers of platinum-based chemotherapy resistance in NSCLC.ResultsThe low expressions of miR-17 and miR-92 families can maintain cisplatin resistance through the regulation of CDKN1A and RAD21. As a result of high expressions of CDKN1A and RAD21, the inhibition of DNA synthesis and the repair of DNA damage are achieved and these may be two major contributing factors to cisplatin resistance. Moreover, we demonstrate that the expressions of miR-17 and miR-92 families in NSCLC tissues are significantly associated with platinum-based chemotherapy response.ConclusionOur study indicates that miR-17 and miR-92 families play important roles in cisplatin resistance and can be used as potential biomarkers for better predicting the clinical response to platinum-based chemotherapy in NSCLC.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1713-z) contains supplementary material, which is available to authorized users.
Highlights
Chemotherapy is an important therapeutic approach for non-small cell lung cancer (NSCLC)
Low expressions of miR-17 and miR-92 families are associated with cisplatin resistance Generally, miRNAs are produced from several genomic miRNA gene clusters and can be classified into different miRNA family based on the 6-nucleotide seed sequence similarities
We have examined the expression levels of miRNAs in cisplatin-resistant cells (A549/DDP cells) and cisplatinsensitive cells (A549 cells) using the microarray analysis assay in our previous study (20)
Summary
Chemotherapy is an important therapeutic approach for non-small cell lung cancer (NSCLC). A successful long-term treatment can be prevented by the occurring of chemotherapy resistance frequently, and the molecular mechanisms of chemotherapy resistance in NSCLC remain unclear. Abnormal expressions of miR-17 and miR-92 families are observed in cisplatin-resistant cells, suggesting that miR-17 and miR-92 families are involved in the regulation of cisplatin resistance in NSCLC. The research of chemotherapy resistance is important for the successful chemotherapy of NSCLC. MicroRNA (miRNA) is a kind of endogenous small non-coding RNA, and it has been found that miRNAs play important roles in the regulation of gene expression at the post-transcriptional level through base pairing to the 3’ untranslated region (3’-UTR) of target messenger RNA (mRNA) [6]. The miR-17 ~ 92 cluster and paralogous, which are recognized as typical oncogene-type miRNAs, have been shown to promote tumorigenesis of many cancer types, such as lung cancer, medulloblastoma, leukaemia, hepatocellular carcinoma and so on [10,11,12]
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