title: Identification of novel deregulated RNA metabolism-related genes in non-small cell lung cancer.
abstract: Lung cancer is a leading cause of cancer death worldwide. Several alterations in RNA metabolism have been found in lung cancer cells; this suggests that RNA metabolism-related molecules are involved in the development of this pathology. In this study, we searched for RNA metabolism-related genes that exhibit different expression levels between normal and tumor lung tissues. We identified eight genes differentially expressed in lung adenocarcinoma microarray datasets. Of these, seven were up-regulated whereas one was down-regulated. Interestingly, most of these genes had not previously been associated with lung cancer. These genes play diverse roles in mRNA metabolism: three are associated with the spliceosome (ASCL3L1, SNRPB and SNRPE), whereas others participate in RNA-related processes such as translation (MARS and MRPL3), mRNA stability (PCBPC1), mRNA transport (RAE), or mRNA editing (ADAR2, also known as ADARB1). Moreover, we found a high incidence of loss of heterozygosity at chromosome 21q22.3, where the ADAR2 locus is located, in NSCLC cell lines and primary tissues, suggesting that the downregulation of ADAR2 in lung cancer is associated with specific genetic losses. Finally, in a series of adenocarcinoma patients, the expression of five of the deregulated genes (ADAR2, MARS, RAE, SNRPB and SNRPE) correlated with prognosis. Taken together, these results support the hypothesis that changes in RNA metabolism are involved in the pathogenesis of lung cancer, and identify new potential targets for the treatment of this disease.
authors.affiliation: Division of Oncology, Center for Applied Medical Research, Pamplona, Spain.
authors.forename: Iñaki
authors.initials: I
authors.lastname: Valles
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Pajares
authors.forename: Victor
authors.initials: V
authors.lastname: Segura
authors.forename: Elisabet
authors.initials: E
authors.lastname: Guruceaga
authors.forename: Javier
authors.initials: J
authors.lastname: Gomez-Roman
authors.forename: David
authors.initials: D
authors.lastname: Blanco
authors.forename: Akiko
authors.initials: A
authors.lastname: Tamura
authors.forename: Luis M
authors.initials: LM
authors.lastname: Montuenga
authors.forename: Ruben
authors.initials: R
authors.lastname: Pio
mesh_terms: D000243:Adenosine Deaminase / Q000235:genetics; D000368:Aged; D000369:Aged, 80 and over; D017398:Alternative Splicing / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019656:Loss of Heterozygosity; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D011379:Prognosis; D012313:RNA / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics
chemical_list: D016601:RNA-Binding Proteins; D012313:RNA; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase