Kuang Qiwen, Liang Yuxiang, Zhuo Yangjia, Cai Zhiduan, Jiang Funeng, Xie Jianjiang, Zheng Yu, Zhong Weide
Department of Urology, Guangdong Provincial Institute of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, People's Republic of China.
Onco Targets Ther. 2021 May 24;14:3353-3366. doi: 10.2147/OTT.S290284. eCollection 2021.
ALDOA plays an essential role in cancer progression in different human cancers; however, its function has not been understood in prostate cancer (PCa).
Associations of ALDOA expression with clinicopathological features and patient prognosis in PCa were evaluated based on data obtained from the Taylor database and our clinical tissue microarray. The potential roles of ALDOA in malignant progression were verified using a series of in vivo and in vitro experiments after stable ALDOA overexpression and knockdown in DU145 and PC3 cell lines. An aldolase A inhibitor was used to determine the effects of inhibition of ALDOA on PCa cell proliferation.
Higher expression of ALDOA was positively correlated with the incidence of postoperative metastasis and biochemical recurrence (BCR) and may predict poor prognosis in PCa patients. In vivo experiments demonstrated that overexpression of ALDOA could significantly promote cell proliferation, prolong the cell cycle, and significantly reduce the apoptosis rate of PCa cells. Knockdown of expression of ALDOA could inhibit the proliferation and shorten the cell cycle of PCa cells significantly, with no significant effects on cell apoptosis ( > 0.05). In vitro experiments showed that overexpression of ALDOA could significantly promote tumor growth ( < 0.05), while treatment with the Aldolase A inhibitor naphthol AS-E phosphate dose-dependently suppressed the growth of PCa cells ( < 0.01). The analysis of datasets from the Taylor database showed that there was negative regulatory relationship between the expression of ALDOA and MYPT1 ( < 0.001).
Our study revealed that ALDOA played an important role in the progression of PCa. The MYPT1-ALDOA signaling axis may be a new target for the clinical treatment of PCa patients given its negative regulatory relationship. Our study suggests that Aldolase A inhibitors may represent a novel approach to inhibit the growth of PCa.
醛缩酶A（ALDOA）在不同人类癌症的进展中起重要作用；然而，其在前列腺癌（PCa）中的功能尚未明确。
基于从泰勒数据库和我们的临床组织芯片获得的数据，评估ALDOA表达与PCa临床病理特征及患者预后的相关性。在DU145和PC3细胞系中稳定过表达和敲低ALDOA后，通过一系列体内和体外实验验证ALDOA在恶性进展中的潜在作用。使用醛缩酶A抑制剂来确定抑制ALDOA对PCa细胞增殖的影响。
ALDOA的高表达与术后转移和生化复发（BCR）的发生率呈正相关，并且可能预示PCa患者预后不良。体内实验表明，ALDOA的过表达可显著促进细胞增殖、延长细胞周期，并显著降低PCa细胞的凋亡率。敲低ALDOA的表达可显著抑制PCa细胞的增殖并缩短细胞周期，对细胞凋亡无显著影响（>0.05）。体外实验表明，ALDOA的过表达可显著促进肿瘤生长（<0.05），而用醛缩酶A抑制剂萘酚AS-E磷酸盐处理可剂量依赖性地抑制PCa细胞的生长（<0.01）。对泰勒数据库数据集的分析表明，ALDOA和MYPT1的表达之间存在负调控关系（<0.001）。
我们的研究表明，ALDOA在PCa进展中起重要作用。鉴于其负调控关系，MYPT1-ALDOA信号轴可能是PCa患者临床治疗的新靶点。我们的研究表明，醛缩酶A抑制剂可能代表一种抑制PCa生长的新方法。
