下调 U2AF1 促进 ARV7 剪接和前列腺癌进展。

Down regulation of U2AF1 promotes ARV7 splicing and prostate cancer progression.

机构信息

Surgical Department I (Urology Department), Longhua Hospital Shanghai University of Traditional Chinese Medicine, No. 725 Wanping Road South, Xuhui District, Shanghai, 200032, China.

出版信息

Biochem Biophys Res Commun. 2021 Feb 19;541:56-62. doi: 10.1016/j.bbrc.2020.12.111. Epub 2021 Jan 19.

DOI:10.1016/j.bbrc.2020.12.111

PMID:33477033

Abstract

The present study aims to investigate the roles of U2 Small Nuclear RNA Auxiliary Factor 1 (U2AF1) in the resistance to anti-androgen treatment in prostate cancer and its underlying mechanism. U2AF1 and androgen receptor variant 7 (ARV7) knockdown and overexpression were introduced in PC3 and DU145 cells. In addition, a bicalutamide-resistant PC3 (PC3 BR) cell line was also constructed. Cell count, MTT and soft agar colony formation assays were performed to evaluate cell proliferation. qRT-PCR was applied to determine the mRNA levels of U2AF1, ARV7 and Mitogen-Activated Protein Kinase 1 (MAPK1). Western blot was used to determine the MAPK1 protein expression. A negative correlation between ARV7 and U2AF1 in prostate tumor tissues was observed. U2AF1 downregulation was correlated with poor prognosis in prostate cancer patients. U2AF1 exhibited a negative correlation with ARV7 and its downregulation promoted prostate cancer cell proliferation and bicalutamide resistance. The regulatory effects of U2AF1 on ARV7 splicing were associated with MAPK1. U2AF1 affected prostate cancer proliferation and anti-androgen resistance by regulating ARV7 splicing.

摘要

本研究旨在探讨 U2 小核 RNA 辅助因子 1（U2AF1）在前列腺癌对抗雄激素治疗耐药中的作用及其潜在机制。在 PC3 和 DU145 细胞中敲低和过表达 U2AF1 和雄激素受体变体 7（ARV7），并构建了比卡鲁胺耐药 PC3（PC3 BR）细胞系。通过细胞计数、MTT 和软琼脂集落形成实验评估细胞增殖。qRT-PCR 用于测定 U2AF1、ARV7 和丝裂原活化蛋白激酶 1（MAPK1）的 mRNA 水平。Western blot 用于测定 MAPK1 蛋白表达。观察到前列腺肿瘤组织中 ARV7 和 U2AF1 之间存在负相关。U2AF1 的下调与前列腺癌患者的不良预后相关。U2AF1 与 ARV7 呈负相关，其下调促进了前列腺癌细胞增殖和比卡鲁胺耐药。U2AF1 对 ARV7 剪接的调控作用与 MAPK1 有关。U2AF1 通过调节 ARV7 剪接影响前列腺癌的增殖和抗雄激素耐药性。