The ALDOA Metabolism Pathway as a Potential Target for Regulation of Prostate Cancer Proliferation

Abstract

Qiwen Kuang,1,* Yuxiang Liang,2,* Yangjia Zhuo,2,* Zhiduan Cai,3 Funeng Jiang,2 Jianjiang Xie,2 Yu Zheng,4 Weide Zhong1,2,5,6 1Department of Urology, Guangdong Provincial Institute of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2Department 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; 3Department of Urology, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China; 4Department of Urology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, People’s Republic of China; 5Department of Urology, Dejiang County People’s Hospital of Guizhou Province, Dejiang, Guizhou, People’s Republic of China; 6School of Medicine, Jinan University, Guangzhou, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Weide ZhongDepartment of Urology, Guangdong Provincial Institute of Nephrology, Nanfang Hospital, Southern Medical University, 1838, Guangzhoudadaobei, Baiyun District, Guangzhou, People’s Republic of ChinaTel [phone]Fax [phone]Email [email protected]: ALDOA plays an essential role in cancer progression in different human cancers; however, its function has not been understood in prostate cancer (PCa).Methods: 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.Results: 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 (P > 0.05). In vitro experiments showed that overexpression of ALDOA could significantly promote tumor growth (P < 0.05), while treatment with the Aldolase A inhibitor naphthol AS-E phosphate dose-dependently suppressed the growth of PCa cells (P < 0.01). The analysis of datasets from the Taylor database showed that there was negative regulatory relationship between the expression of ALDOA and MYPT1 (P < 0.001).Conclusion: 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.Keywords: prostate cancer, ALDOA, aldolase A, tumor growth, metastasis

Keywords

• prostate cancer
• aldoa
• aldolase a
• tumor growth
• metastasis