title: mRNA and microRNA expression profiles of radioresistant NCI-H520 non-small cell lung cancer cells.
abstract: To elucidate the mechanism of radioresistance in non-small cell lung cancer (NSCLC) cells and to identify key molecules conferring radioresistance, the radioresistant subclone NCI-H520/R, derived from the NCI-H520 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 4 x 44 k Oligo microarray and Agilent Human miRCURY(™) LNA array, and confirmed by reverse transcription-quantitative polymerase chain reaction. Pathway analysis and Gene Ontology (GO) analysis were performed to determine the biological functions of the subset of differentially expressed genes. miRNA-mRNA correlation analysis between the expression levels of each miRNA and all its predicted target genes was performed to further understand the radioresistance in the NCI-H520 cells. Following eight rounds of sublethal irradiation, a total of 2,862 mRNAs were significantly differentially expressed in the NCI-H520/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 NCI-H520/R cells. Multiple core regulatory processes and signaling pathways were identified as being of likely relevance to radioresistance in NCI-H520/R cells, including the mitogen-activated 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.
authors: Ultrasound Diagnosis Department, Shandong Cancer Hospital and Institute, Jinan, Shandong 250117, P.R. China.
authors: Wei
authors: W
authors: Guo
authors: Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, Shandong 250117, P.R. China.
authors: Li
authors: L
authors: Xie
authors: Ultrasound Diagnosis Department, Shandong Cancer Hospital and Institute, Jinan, Shandong 250117, P.R. China.
authors: Long
authors: L
authors: Zhao
authors: Ultrasound Diagnosis Department, Shandong Cancer Hospital and Institute, Jinan, Shandong 250117, P.R. China.
authors: Yuehuan
authors: Y
authors: Zhao
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000528:radiation effects; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism*; D011836:Radiation Tolerance / Q000235:genetics; D011839:Radiation, Ionizing; D060888:Real-Time Polymerase Chain Reaction; D059467:Transcriptome / Q000528:radiation effects*; D015854:Up-Regulation / Q000528:radiation effects
chemical_list: D035683:MicroRNAs; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D020928:Mitogen-Activated Protein Kinases