PCBP1 protects bladder cancer cells from mitochondria injury and ferroptosis by inducing LACTB mRNA degradation.

Although Poly C Binding Protein 1 (PCBP1) affects cellular ferroptosis and mitochondrial dysfunction, the mechanisms by which PCBP1 regulates bladder cancer (BC) cell functions are unknown. In this study, two BC cell lines (T24 and UMUC3) were treated with different doses of ferroptosis inducer erastin to analyze the effect of PCBP1. Online databases (RPISeq and CatRAPID) were used to predict the possible direct interaction between PCBP1 protein and serine ß-lactamase-like protein (LACTB) mRNA, which was further validated via RNA pull-down, RNA immunoprecipitation, and luciferase reporter assays. Mitochondria injury and ferroptosis were evaluated using CCK-8 assay, TUNEL staining, flow cytometry, corresponding kits, and JC-1 staining. In vivo experiments were conducted using tumor xenograft models. Quantitative reverse-transcription polymerase chain reaction was used to detect transcript expression levels, while protein levels were analyzed using western blot and immunohistochemistry. PCBP1 expression was significantly upregulated in BC tissues and cell lines. Also, PCBP1 knockdown increased erastin-mediated ferroptosis in T24 and UMUC3 cells, while PCBP1 overexpression decreased erastin-mediated ferroptosis in T24 and UMUC3 cells. Mechanistic results showed that LACTB mRNA is a novel PCBP1-binding transcript. LACTB upregulation promoted erastin-induced ferroptosis and mitochondrial dysfunction. Furthermore, LACTB overexpression reversed PCBP1-mediated ferroptosis protection, including decreased ROS and enhanced mitochondrial function, which were further alleviated after phosphatidylserine decarboxylase (PISD) overexpression. Moreover, PCBP1 silencing significantly enhanced tumor inhibition effect of sulfasalazine in xenograft mice transplanted with T24 and UMUC3 cells, leading to LACTB upregulation and PISD downregulation. In conclusion, PCBP1 protects BC cells against mitochondria injury and ferroptosis via LACTB/PISD axis.

Primary Urothelium Carcinoma of the Distal Urethra in a Male: Case Report and Literature Review.

Male primary urethral urothelium carcinoma is a rare clinical case. Here, we detail a case of a 58-year-old man with primary urothelium carcinoma of the distal urethra treated in our hospital. The patient with a neoplasm inside the external urethral orifice for 2 years, which was previously diagnosed as condyloma acuminata, had received photodynamic therapy for 3 times, with initial symptoms of urinary stream bifurcation and dysuria. The exfoliative urine cytology showed negative. Cystoscopy showed a tumor growing around the distal urethra. Biopsy and immunohistochemistry revealed high-grade papillary urothelium carcinoma. The patient received partial urethrectomy, followed by urinary bladder irrigation chemotherapy with epirubicin postoperatively. The corpus spongiosum was invaded while the corpus cavernosa were not. Postoperative pathological examination showed high-grade invasive urothelium carcinoma. There is no evidence of tumor recurrence, metastasis or surgical complications during a 61-month follow-up period. Male primary urethral urothelium carcinoma is a rare clinical case with particular clinical and pathological characteristics. There are still no established treatment guidelines and should be studied further.