RESUMEN
Circular RNAs (circRNAs) take on regulatory roles in renal cell carcinoma (RCC). The research's goal was to figure out circ-CSPP1's role and molecular mechanism in RCC. The results clarified that circ-CSPP1 expression was enhanced in RCC. Down-regulating circ-CSPP1 refrained the proliferation, migration, invasion, and Warburg effect (aerobic glycolysis), but accelerated apoptosis of RCC cells. The luciferase activity assay exhibited that circ-CSPP1 could perform as an endogenous sponge for miR-493-5p. Elevating miR-493-5p repressed RCC progression. The bioinformatics website starBase confirmed that ras-related C3 botulinum toxin substrate 1 (RAC1) was a target gene of miR-493-5p. Circ-CSPP1 up-regulated RAC1 by sponging miR-493-5p, and elevating RAC1 could turn around the effect of down-regulating circ-CSPP1 on RCC cells. Taken together, circ-CSPP1 is identified as a novel RCC-promoting RNA that could serve as a latent therapeutic target for RCC therapy.
Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , MicroARNs , Humanos , ARN Circular/genética , Carcinoma de Células Renales/genética , Carcinogénesis/genética , Neoplasias Renales/genética , MicroARNs/genética , Proteína de Unión al GTP rac1/genética , Proteínas Asociadas a Microtúbulos , Proteínas de Ciclo CelularRESUMEN
Docetaxel resistance is one of the major obstacles that undermine the treatment outcome of PCa. Exploring molecular mechanisms associated with docetaxel resistance could provide insights into the formulation of novel strategies enhancing the efficacy of PCa treatment. Ladinin-1 (LAD1) is an anchoring filament protein in basement membranes, which contributes to the association of the epithelial cells with the underlying mesenchyme. LAD1 has been implicated in the progression of different cancers. However, its role in PCa remains to be investigated. In the present study, we found that LAD1 was highly expressed in docetaxel-resistant PCa cells, while its expression was significantly suppressed in tumor samples after docetaxel treatment. Moreover, the expression level of LAD1 in PCa tissues was significantly higher than that of normal tissue, and high expression level of LAD1 was significantly associated with adverse outcomes of PCa patients. Finally, high expression of LAD1 in PCa tissue was also correlated with the expression level of genes involving in tumor cell proliferation and invasive behaviors. Collectively, our data suggest that LAD1 may serve as a potential prognostic factor in PCa patients.
Asunto(s)
Docetaxel/farmacología , Resistencia a Antineoplásicos/genética , Glicoproteínas de Membrana/genética , Neoplasias de la Próstata , Línea Celular Tumoral , Humanos , Masculino , Glicoproteínas de Membrana/metabolismo , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/mortalidadRESUMEN
Many studies have reported the role of xeroderma pigmentosum group D (XPD) with prostate cancer risk, but the results remained controversial. To derive a more precise estimation of the relationship, a meta-analysis was performed. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association between XPD Asp312Asn and Lys751Gln polymorphisms and prostate cancer risk. A total of 8 studies including 2620 cases and 3225 controls described Asp312Asn genotypes, among which 10 articles involving 3230 cases and 3582 controls described Lys751Gln genotypes and were also involved in this meta-analysis. When all the eligible studies were pooled into this meta-analysis, a significant association between prostate cancer risk and XPD Asp312Asn polymorphism was found. For Asp312Asn polymorphism, in the stratified analysis by ethnicity and source of controls, prostate cancer risk was observed in co-dominant, dominant and recessive models, while no evidence of any associations of XPD Lys751Gln polymorphism with prostate cancer was found in the overall or subgroup analyses. Our meta-analysis supports that the XPD Asp312Asn polymorphism contributed to the risk of prostate cancer from currently available evidence. However, a study with a larger sample size is needed to further evaluate gene-environment interaction on XPD Asp312Asn and Lys751Gln polymorphisms and prostate cancer risk.