RESUMO
Retinoids are signaling molecules that control a wide variety of cellular processes and possess antitumor activity. This work presents a comprehensive description of changes in the expression of 23 genes that regulate retinoid metabolism and signaling in non-small-cell lung cancer tumors compared to adjacent normal tissues obtained using RT-PCR. Even at early stages of malignant transformation, a significant decrease in ADH1B, ADH3, RDHL, and RALDH1 mRNA levels was observed in 82, 79, 73, and 64% of tumor specimens, respectively, and a considerable increase in AKR1B10 mRNA content was observed in 80% of tumors. Dramatic changes in the levels of these mRNAs can impair the synthesis of all-trans retinoic acid, a key natural regulatory retinoid. Apart from that, it was found that mRNA levels of nuclear retinoid receptor genes RXRγ, RARα, RXRα, and gene RDH11 were significantly decreased in 80, 67, 57, and 66% of tumor specimens, respectively. Thus, neoplastic transformation of lung tissue cells is accompanied with deregulated expression of key genes of retinoid metabolism and function.
Assuntos
3-Hidroxiesteroide Desidrogenases/biossíntese , Álcool Desidrogenase/biossíntese , Aldeído Desidrogenase/biossíntese , Aldeído Redutase/biossíntese , Carcinoma Pulmonar de Células não Pequenas/genética , 3-Hidroxiesteroide Desidrogenases/genética , Álcool Desidrogenase/genética , Aldeído Desidrogenase/genética , Família Aldeído Desidrogenase 1 , Aldeído Redutase/genética , Aldo-Ceto Redutases , Carcinoma Pulmonar de Células não Pequenas/patologia , Transformação Celular Neoplásica/genética , Regulação Neoplásica da Expressão Gênica , Humanos , RNA Mensageiro/biossíntese , Receptores do Ácido Retinoico/biossíntese , Receptores do Ácido Retinoico/genética , Retinal Desidrogenase , Receptor alfa de Ácido Retinoico , Retinoides/genética , Retinoides/metabolismo , Transdução de Sinais/genética , Tretinoína/metabolismoRESUMO
Glycolysis is a main catabolic pathway of glucose metabolism, accompanied by ATP synthesis. More than 30 enzymes are involved in glycolysis, and genes that encode them can be considered housekeeping genes due to the high conservatism and evolutionary antiquity of the process. We studied the expression of these genes in kidney papillary cancer and planocellular lung cancer via the bioinformatic analysis of transcriptome database and method of quantitative real time PCR. Quantitative analysis of mRNA level demonstrated that only a part ofgenes that encode glycolysis enzymes maintain relatively stable mRNA level, including the HK1, ADPGK, GPI, PGK1, and PKM2 genes in kidney papillary cancer and the ADPGK, ALDOA, GAPDH, PGK1, BPGM, ENO1, and PKM2 genes in planocellular lung cancer. The frequent increase in the mRNA expression of PFKP, ALDOA, and GAPDH genes in kidney cancer, as well as the GPI gene in lung cancer, were detected for the first time by real time PCR. For other genes, their differential expression was demonstrated; the cases of both a decrease and increase in the mRNA level were detected. Thus, several genes that can be used as control genes in transcriptome analysis by real time PCR in kidney and lung cancer, as well as a number of differentially expressed genes that can be potential oncomarkers, were identified.
