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PRPF19 functions in DNA damage repair and gemcitabine sensitivity via regulating DDB1 in bladder cancer cells

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Abstract

PRPF19 seems to play either tumor-promoting or anti-tumor roles depending on cancer types. This study aimed to clarify the potential role and mechanism of PRPF19 in bladder cancer. PRPF19 expression and its correlation with patients’ overall survival were analyzed in bladder cancer. The effects of PRPF19 on the viability, apoptosis, DNA damage repair, and gemcitabine sensitivity in human bladder cancer cells (T24 and 5637) were analyzed through loss- or gain-of-function methods. Moreover, the influences of DDB1 small interfering RNA on these indexes were evaluated in bladder cancer cells. At last, rescue experiment using DDB1 overexpression was carried out to confirm whether PRPF19 functioned via regulating DDB1. PRPF19 was highly expressed in bladder cancer tissues and cells. Elevated PRPF19 expression was related to shorter overall survival of bladder cancer patients. Downregulation of PRPF19 inhibited cell proliferation, promoted cell apoptosis, increased the number of γ-H2AX-positive cells, and reduced the mRNA and protein levels of DDB1 and BRCA1. Meanwhile, knockdown of PRPF19 decreased the IC50 of gemcitabine and promoted gemcitabine-induced cell apoptosis. Whereas, PRPF19 overexpression significantly decreased gemcitabine-induced apoptosis in bladder cancer cells. DDB1 downregulation suppressed cell proliferation and BRCA1 expression, but elevated the number of γ-H2AX-positive cells and gemcitabine sensitivity. Upregulation of DDB1 attenuated γ-H2AX-positive cell number, BRCA1 expression and IC50 of gemcitabine that were affected by PRPF19 silencing. In conclusion, PRPF19 expression was upregulated in bladder cancer. It promoted cell growth and DNA damage repair, and decreased gemcitabine sensitivity via positively regulating DDB1 expression.

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Authors and Affiliations

  1. Department of Urology Surgery, The Affiliated People’s Hospital of Ningbo University, No. 251, Baizhang East Road, Yinzhou District, Ningbo, 315000, China

    Jingjiang Yu

  2. Department of Vascular Surgery, The Affiliated People’s Hospital of Ningbo University, Ningbo, 315000, China

    Shuxiong Ge

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  1. Jingjiang Yu
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JY and SG designed the study, conducted the experiments, collected and analyzed the data. JY wrote the original manuscript. All authors reviewed the manuscript.

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Correspondence to Jingjiang Yu.

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10616_2023_599_MOESM1_ESM.jpeg

BRCA1 expression in bladder cancer tissues and normal samples in TCGA database predicted by Starbase v3.0 software. Supplementary material 1 (JPEG 69.7 kb)

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Yu, J., Ge, S. PRPF19 functions in DNA damage repair and gemcitabine sensitivity via regulating DDB1 in bladder cancer cells. Cytotechnology 76, 85–96 (2024). https://doi.org/10.1007/s10616-023-00599-7

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