mRNA and microRNA expression profiles of radioresistant NCIH520 nonsmall cell lung cancer cells

To elucidate the mechanism of radioresistance in nonsmall cell lung cancer (NSCLC) cells and to identify key molecules conferring radioresistance, the radioresistant subclone NCIH520/R, derived from the NCIH520 NSCLC cell line, was established with eight rounds of sublethal irradiation. The radioresistant features were subsequently assessed using a clonogenic assay, analysis of apoptosis and an MTT assay, the gene expression levels were examined using an Agilent Whole Human Genome 4x44 k Oligo microarray and Agilent Human miRCURY™ LNA array, and confirmed by reverse transcriptionquantitative polymerase chain reaction. Pathway analysis and Gene Ontology (GO) analysis were performed to determine the biological functions of the subset of differentially expressed genes. miRNAmRNA correlation analysis between the expression levels of each miRNA and all its predicted target genes was performed to further understand the radioresistance in the NCIH520 cells. Following eight rounds of sublethal irradiation, a total of 2,862 mRNAs were significantly differentially expressed in the NCIH520/R cells, including 893 upregulated genes and 1,969 downregulated genes. A total of 162 upregulated miRNAs and 274 downregulated miRNAs were significantly deregulated in the NCIH520/R cells. Multiple core regulatory processes and signaling pathways were identified as being of likely relevance to radioresistance in NCIH520/R cells, including the mitogenactivated protein kinase signaling pathway and neurotrophin signaling pathway. The expression of genes associated with radioresistance reflects the complex biological processes involved in clinical cancer cell eradication and requires further investigation for future enhancement of therapy.