Analysis of novel microRNA targets in drug-sensitive and -insensitive small cell lung cancer cell lines.

Abstract

Advances in chemotherapy have failed to improve the long-term survival rate of small cell lung cancer (SCLC) patients due to multidrug resistance (MDR). The mechanisms of MDR are complex involving multiple genes and a variety of mechanisms. MicroRNAs (miRNAs) are non-coding RNAs theoretically involved in gene regulation. The aim of the present study was to explore the role of miRNAs in SCLC occurrence and multidrug resistance. Expression levels of known miRNAs in SCLC cell line H446 and its multidrug-resistant cell line H446/CDDP were analyzed using the next generation high through-put Illumina Solexa sequencing technology, and expression of a group of specific miRNAs was validated by quantitative polymerase chain reaction (qPCR). Furthermore, novel miRNAs and their putative target genes in the two SCLC cell lines were predicted with the help of software developed by Beijing Genomics Institute and analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The results revealed a set of known miRNAs with altered expression in the H446 and H446/CDDP cells which may be associated with multidrug resistance of SCLC. Biological information analysis of the novel miRNAs and their putative target genes further elucidated the role of miRNAs in MDR. In addition, the pathway prediction by KEGG analysis may provide clues for further research on MDR of SCLC.