RESUMO
NKX3.1 and PTEN genes are involved in the development and progression of prostate cancer (PCa). Here, in line with other studies that correlated the expression of these two genes, we aimed at evaluating the expression pattern of these genes in clinical PCa samples. Collectively, 81 tissue samples including 45 human PCa and 36 benign prostatic hyperplasia (BPH) specimens were included in the study. The tissue samples were subjected to RNA extraction and subsequently to cDNA synthesis according to the kit manufacturer's protocol. Quantitative Real-Time PCR assay was performed for each sample in triplicate reactions. REST and SPSS software were used to statistically analyze PTEN and NKX3.1 gene expression data. Expression level of both NKX3.1 and PTEN genes was down-regulated in PCa samples compared to BPH samples. The relative expression ratio of PTEN and NKX3.1 was decreased to 0.155 and 0.003, respectively (P=0.000). The results of Chi-Square analysis revealed a significant correlation between the expression of these genes in both BPH and cancer groups (P=0.004 and 0.001, respectively). According to previous studies and our data, we concluded that the association between the down-regulation of PTEN and NKX3.1 genes contributed to the prostate tumorigenesis. This might highlight the interaction between the proteins encoded by these genes. Furthermore, this finding might be exploited for the development of innovative diagnostic and therapeutic approaches in PCa.
Assuntos
Regulação para Baixo , Expressão Gênica , Proteínas de Homeodomínio/genética , PTEN Fosfo-Hidrolase/genética , Neoplasias da Próstata/genética , Fatores de Transcrição/genética , Idoso , Idoso de 80 Anos ou mais , Carcinogênese/genética , Progressão da Doença , Eletroforese em Gel Bidimensional , Marcadores Genéticos , Proteínas de Homeodomínio/análise , Humanos , Masculino , Pessoa de Meia-Idade , PTEN Fosfo-Hidrolase/análise , Reação em Cadeia da Polimerase em Tempo Real , Valores de Referência , Temperatura , Fatores de Transcrição/análise , Temperatura de TransiçãoRESUMO
ABSTRACT NKX3.1 and PTEN genes are involved in the development and progression of prostate cancer (PCa). Here, in line with other studies that correlated the expression of these two genes, we aimed at evaluating the expression pattern of these genes in clinical PCa samples. Collectively, 81 tissue samples including 45 human PCa and 36 benign prostatic hyperplasia (BPH) specimens were included in the study. The tissue samples were subjected to RNA extraction and subsequently to cDNA synthesis according to the kit manufacturer's protocol. Quantitative Real-Time PCR assay was performed for each sample in triplicate reactions. REST and SPSS software were used to statistically analyze PTEN and NKX3.1 gene expression data. Expression level of both NKX3.1 and PTEN genes was down-regulated in PCa samples compared to BPH samples. The relative expression ratio of PTEN and NKX3.1 was decreased to 0.155 and 0.003, respectively (P=0.000). The results of Chi-Square analysis revealed a significant correlation between the expression of these genes in both BPH and cancer groups (P=0.004 and 0.001, respectively). According to previous studies and our data, we concluded that the association between the down-regulation of PTEN and NKX3.1 genes contributed to the prostate tumorigenesis. This might highlight the interaction between the proteins encoded by these genes. Furthermore, this finding might be exploited for the development of innovative diagnostic and therapeutic approaches in PCa.
Assuntos
Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Regulação para Baixo , Expressão Gênica , Proteínas de Homeodomínio/genética , PTEN Fosfo-Hidrolase/genética , Neoplasias da Próstata/genética , Fatores de Transcrição/genética , Carcinogênese/genética , Progressão da Doença , Eletroforese em Gel Bidimensional , Marcadores Genéticos , Proteínas de Homeodomínio/análise , PTEN Fosfo-Hidrolase/análise , Reação em Cadeia da Polimerase em Tempo Real , Valores de Referência , Temperatura , Temperatura de Transição , Fatores de Transcrição/análiseRESUMO
The long-lasting inadequacy of existing treatments for prostate cancer has led to increasing efforts for developing novel therapies for this disease. MicroRNAs (miRNAs) are believed to have considerable therapeutic potential due to their role in regulating gene expression and cellular pathways. Identifying miRNAs that efficiently target genes and pathways is a key step in using these molecules for therapeutic purposes. Moreover, computational methods have been devised to help identify candidate miRNAs for each gene/pathway. MAPK and JAK/STAT pathways are known to have essential roles in cell proliferation and neoplastic transformation in different cancers including prostate cancer. Herein, we tried to identify miRNAs that target these pathways in the context of prostate cancer as therapeutic molecules. Genes involved in these pathways were analyzed with various algorithms to identify potentially targeting miRNAs. miR-23a and miR-23b were then selected as the best potential candidates that target a higher number of genes in these pathways with greater predictive scores. We then analyzed the expression of candidate miRNAs in LNCAP and PC3 cell lines as well as prostate cancer clinical samples. miR-23a and miR-23b showed a significant downregulation in cell line and tissue samples, a finding which is consistent with overactivation of these pathways in prostate cancer. In addition, we overexpressed miR-23a and miR-23b in LNCAP and PC3 cell lines, and these two miRNAs decreased IL-6R expression which has a critical role in these pathways. These results suggest the probability of utilizing miR-23a and miR-23b as therapeutic targets for the treatment of prostate cancer.
Assuntos
Biomarcadores Tumorais/biossíntese , MicroRNAs/biossíntese , Neoplasias da Próstata/genética , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Biologia Computacional , Regulação Neoplásica da Expressão Gênica , Humanos , Janus Quinases/genética , Masculino , MicroRNAs/genética , Quinases de Proteína Quinase Ativadas por Mitógeno/genética , Neoplasias da Próstata/patologia , Fatores de Transcrição STAT/genética , Transdução de Sinais/genéticaRESUMO
Complex molecular changes that occur during prostate cancer (PCa) progression have been described recently. Whole genome sequencing of primary PCa samples has identified recurrent gene deletions and rearrangements in PCa. Specifically, these molecular events disrupt the gene loci of phosphatase and tensin homolog (PTEN) and membrane-associated guanylate kinase inverted-2 (MAGI2). In the present study, we analyzed the expression profile of MAGI2 gene in a cohort of clinical PCa (n = 45) and benign prostatic hyperplasia (BPH) samples (n = 36) as well as three PCa cell lines. We also studied the expression of PCa-related genes, including PTEN, NKX3.1, SPINK1, DD3, AMACR, ERG, and TMPRSS2-ERG fusion in the same samples. The expression of MAGI2 mRNA was significantly down-regulated in PC3, LNCaP and DU-145 PCa cell lines (p = 0.000), and also in clinical tumor samples (Relative expression = 0.307, p = 0.002, [95 % CI 0.002-12.08]). The expression of PTEN, NKX3.1, SPINK1, DD3, and AMACR genes was significantly deregulated in prostate tumor samples (p range 0.000-0.044). A significant correlation was observed between MAGI2 and NKX3.1 expression in tumor samples (p = 0.006). Furthermore, the inclusion of MAGI2 in the gene panel improved the accuracy for discrimination between PCa and BPH samples with the sensitivity and specificity of 0.88 [CI 0.76-0.95] and 0.83 [CI 0.68-0.92], respectively. The data presented here suggest that MAGI2 gene can be considered as a novel component of gene signatures for the detection of PCa.
