Xu Xiaolin, Zhu Xin, Liu Feng, Lu Wenlong, Wang Yihan, Yu Jianjun
Department of Urology, The Sixth People's Hospital South Campus Affiliated to Shanghai Jiaotong University, Shanghai, China.
Department of Urology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Transl Androl Urol. 2021 Feb;10(2):900-914. doi: 10.21037/tau-21-53.
The aims of this study were to detect the level of histone crotonylation in prostate cancer (PCa) tissues, analyze the correlations between its level and clinical stage and grade, and explore the effects of bromodomain-containing protein 4 (BRD4) inhibitors and sodium crotonate on the histone crotonylation in PCa cell lines and on the functions of PCa cells.
PCa tissues from 72 patients and adjacent tissues from 7 patients were collected, and immunohistochemistry was used to measure the level of histone crotonylation. Three human PCa cell lines, PC-3, LNCaP, and C42B, were selected and treated with IC50 value of I-BET762, I-BET726, and CPI-203, respectively. Next, short hairpin RNA (shRNA) transient knockdown was used to inhibit BRD4 expression. Histone crotonylation level and the expression of acetylase were determined by Western blotting. Finally, cell proliferation, migration, and invasion were measured with Cell Counting Kit-8 assay, scratch test, and Transwell test respectively.
The level of histone crotonylation in PCa tissue was higher than that in adjacent tissues, and histone lysine crotonylation (Kcr) increased with the increasing malignancy of PCa. Treatments with I-BET762, I-BET726, and CPI-203 could inhibit the proliferation, migration, and invasion of PCa cell lines including PC-3, LNCaP, and C42B, and could also regulate the histone crotonylation and androgen receptor signaling pathways via the regulation of BRD4 expression.
PCa is closely related to histone crotonylation. Inhibition of BRD4 expression can inhibit the proliferation, migration, and invasion of PCa cells.
本研究旨在检测前列腺癌（PCa）组织中组蛋白巴豆酰化水平，分析其水平与临床分期和分级之间的相关性，并探讨含溴结构域蛋白4（BRD4）抑制剂和巴豆酸钠对PCa细胞系中组蛋白巴豆酰化及PCa细胞功能的影响。
收集72例患者的PCa组织和7例患者的相邻组织，采用免疫组织化学法检测组蛋白巴豆酰化水平。选择三个人类PCa细胞系PC-3、LNCaP和C42B，分别用I-BET762、I-BET726和CPI-203的半数抑制浓度（IC50）值进行处理。接下来，使用短发夹RNA（shRNA）瞬时敲低来抑制BRD4表达。通过蛋白质免疫印迹法测定组蛋白巴豆酰化水平和乙酰化酶的表达。最后，分别用细胞计数试剂盒-8法、划痕试验和Transwell试验检测细胞增殖迁移和侵袭能力。
PCa组织中组蛋白巴豆酰化水平高于相邻组织，且组蛋白赖氨酸巴豆酰化（Kcr）随着PCa恶性程度的增加而升高。用I-BET762、I-BET726和CPI-203处理可抑制包括PC-3、LNCaP和C42B在内的PCa细胞系的增殖、迁移和侵袭，还可通过调节BRD4表达来调控组蛋白巴豆酰化和雄激素受体信号通路。
PCa与组蛋白巴豆酰化密切相关。抑制BRD4表达可抑制PCa细胞的增殖、迁移和侵袭。
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