Background
Urinary system's most prevalent malignant tumor is bladder cancer. The enzyme pyrroline-5-carboxylate reductase 1 (PYCR1) has pro-tumorigenic characteristics. In the present study, the upstream and downstream regulatory mechanisms of PYCR1 in bladder cancer were investigated.
Conclusions
We demonstrated that lncRNA-RP11-498C9.13 promoted bladder cancer tumorigenesis by stabilizing the mRNA of PYCR1 and promoted ROS-induced mitophagy. The lncRNA-RP11-498C9.13/PYCR1/mitophagy axis was anticipated to be a significant therapeutic target for bladder cancer.
Methods
The relationship between the expression of PYCR1 in bladder cancer and its prognosis was analyzed using a bioinformatics technique. Plasmid transfection and small interfering RNA were utilized to overexpress and silence genes, respectively. Utilizing MTT, colony formation, EdU, and transwell assays, the proliferation and invasiveness of bladder cancer cells were evaluated. Employing an RNA pull-down experiment and RNA immunoprecipitation, the relationship between RNAs was analyzed. Fluorescence in situ hybridization, immunohistochemistry, and western blotting were used to detect protein expression and localization. Flow cytometry was used to identify reactive species (ROS) expression in cells. Mitophagy was detected using immunofluorescence.
Results
PYCR1 was highly expressed in bladder cancer tissue and was related with a poor prognosis for the patient. By binding to PYCR1, the antisense RNA lncRNA-RP11-498C9.13 prevented the degradation of PYCR1 and promoted its production. Down-regulation of lncRNA-RP11-498C9.13 and PYCR1 inhibited the proliferation and invasiveness of bladder cancer cells and decreased tumorigenesis. In addition, it was found that the lncRNA-RP11-498C9.13/PYCR1 axis promoted ROS generation and induced mitophagy in bladder cancer cells. Conclusions: We demonstrated that lncRNA-RP11-498C9.13 promoted bladder cancer tumorigenesis by stabilizing the mRNA of PYCR1 and promoted ROS-induced mitophagy. The lncRNA-RP11-498C9.13/PYCR1/mitophagy axis was anticipated to be a significant therapeutic target for bladder cancer.