Long noncoding RNA 19 (H19) has been shown to promote bladder cancer cell proliferation and metastasis. However, little is known about how miR-675, mature product of H19, contributes to bladder cancer cell proliferation. In this study, we first evaluated the expression of miR-675 in bladder cancer tissues by quantitative real-time PCR (qRT-PCR) and defined its biological functions by flow cytometry and Western blotting. We found that miR-675 expression levels were remarkably increased in bladder cancer tissues as compared with adjacent noncancerous tissues or normal bladder tissue from health donors; moreover, enhanced miR-675 expression was also observed in bladder cancer cell lines. Ectopic expression of H19 significantly increased bladder cancer cell proliferation and miR-675 expression in vitro. Furthermore, overexpression of miR-675 promoted bladder cancer cell proliferation, while suppression of miR-675 induced G1 phase cell cycle arrest and promoted cell apoptosis. Western blotting analysis further identified that miR-675 inhibited p53 activation, decreased the ratio of Bax/Bcl-2 and cyclin D1 expression in bladder cancer cells; those effects may result in the abnormal proliferation of bladder cancer cells. In conclusion, abnormal enhanced miR-675 expression increases bladder cancer growth by regulating p53 activation, and thus may be helpful in the development of effective treatment strategies for bladder cancer.
Objective: XRCC1 is a multi-domain protein associated with bladder cancer. We investigated the relationship between the distribution of XRCC1 polymorphisms (rs915927 and rs2854501) and clinical outcomes following intravesical instillation with epirubicin (EPI) or mitomycin C (MMC). Methods: A TaqMan assay was performed to determine genotypes of 240 individuals diagnosed with bladder cancer. Logistic regression was used to assess the association between polymorphisms and relapse-free survival (RFS) of patients. Quantitative real-time polymerase chain reaction was performed to determine expression of XRCC1 polymorphisms. Survival curves were generated using the Kaplan-Meier method. Results: Risk of bladder cancer recurrence was significantly reduced in patients receiving EPI who had higher incidences of XRCC1 polymorphisms (P=0.009 for rs915927, P=0.001 for rs2854501). In participants administered MMC, results were not statistically significant. Conclusions: Polymorphisms in XRCC1 SNP variants (rs915927 and rs2854501) were associated with improved clinical outcomes following EPI treatment.
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