Song Wan1, Ming Xi1, Hai-Bo Zhao2, Wei Hua1, Yuan-Ling Liu1, Yu-Lin Zhou1, Yang-Jia Zhuo3, Ze-Zhen Liu3, Zhi-Duan Cai3, Yue-Ping Wan4, Wei-De Zhong5. 1. Department of Urology, Huadu District People's Hospital, Southern Medical University, Guangzhou, 510800, China. 2. Guangdong Provincial Institute of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. 3. Guangdong Provincial Institute of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China; Department of Urology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510180, China. 4. Department of Urology, Huadu District People's Hospital, Southern Medical University, Guangzhou, 510800, China. Electronic address: songyouxiang@163.com. 5. Department of Urology, Huadu District People's Hospital, Southern Medical University, Guangzhou, 510800, China; Guangdong Provincial Institute of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China; Department of Urology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510180, China. Electronic address: zhongwd2009@live.cn.
Abstract
BACKGROUND: Accumulating studies reported that 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2) may function as either an oncogene or a tumor suppressor in various human cancers. However, its involvement in prostate cancer (PCa) remains unknown. Therefore, the aim of this study was to investigate the clinical significance of HMGCS2 expression and its functions in PCa. METHODS: Expression levels of HMGCS2 mRNA and protein were detected by quantitative Polymerase Chain Reaction (qPCR), Western blot and immunohistochemistry, respectively. Associations of HMGCS2 expression with various clinicopathological features and patients' prognosis of PCa were statistically evaluated. Roles of HMGCS2 dysregulation in cell proliferation, invasion and migration of PCa cell lines were also determined. RESULTS: HMGCS2 protein expression was significantly reduced in PCa tissues compared to adjacent benign prostate tissues at protein levels (P < 0.05). Clinically, low HMGCS2 mRNA expression was dramatically associated with high Gleason score (GS) and pathological grade, as well as the presence of distant metastasis of PCa patients. In addition, PCa patients with low HMGCS2 mRNA expression more frequently had shorter disease-free survival and biochemical recurrence-free survival (all P < 0.05). HMGCS2 expression was identified as an independent factor to predict both disease-free and biochemical recurrence-free survivals of PCa patients. Moreover, loss-of-function experiments demonstrated that HMGCS2 knockdown-expression promotes cell proliferation, colony formation, invasion and migration of PCa cells in vitro and lower the apoptotic rate of PCa cells in vitro. CONCLUSIONS: Our data indicate that HMGCS2 may be capable of predicting the risk of biochemical recurrence in PCa patients after radical prostatectomy and functions as a tumor suppressor in PCa cancer, implying its related pathway potential as a drug candidate in anti-PCa therapy.
BACKGROUND: Accumulating studies reported that 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2) may function as either an oncogene or a tumor suppressor in various humancancers. However, its involvement in prostate cancer (PCa) remains unknown. Therefore, the aim of this study was to investigate the clinical significance of HMGCS2 expression and its functions in PCa. METHODS: Expression levels of HMGCS2 mRNA and protein were detected by quantitative Polymerase Chain Reaction (qPCR), Western blot and immunohistochemistry, respectively. Associations of HMGCS2 expression with various clinicopathological features and patients' prognosis of PCa were statistically evaluated. Roles of HMGCS2 dysregulation in cell proliferation, invasion and migration of PCa cell lines were also determined. RESULTS:HMGCS2 protein expression was significantly reduced in PCa tissues compared to adjacent benign prostate tissues at protein levels (P < 0.05). Clinically, low HMGCS2 mRNA expression was dramatically associated with high Gleason score (GS) and pathological grade, as well as the presence of distant metastasis of PCa patients. In addition, PCa patients with low HMGCS2 mRNA expression more frequently had shorter disease-free survival and biochemical recurrence-free survival (all P < 0.05). HMGCS2 expression was identified as an independent factor to predict both disease-free and biochemical recurrence-free survivals of PCa patients. Moreover, loss-of-function experiments demonstrated that HMGCS2 knockdown-expression promotes cell proliferation, colony formation, invasion and migration of PCa cells in vitro and lower the apoptotic rate of PCa cells in vitro. CONCLUSIONS: Our data indicate that HMGCS2 may be capable of predicting the risk of biochemical recurrence in PCa patients after radical prostatectomy and functions as a tumor suppressor in PCa cancer, implying its related pathway potential as a drug candidate in anti-PCa therapy.
Authors: Ha T N Nguyen; Haoliang Xue; Virginie Firlej; Yann Ponty; Melina Gallopin; Daniel Gautheret Journal: BMC Cancer Date: 2021-04-12 Impact factor: 4.430