J Cancer 2021; 12(1):232-243. doi:10.7150/jca.49560

Research Paper

Down-regulation of ACACA suppresses the malignant progression of Prostate Cancer through inhibiting mitochondrial potential

Hui Zhang1*, Shaoyou Liu2*, Zhouda Cai1*, Weimin Dong1, Jianheng Ye1, Zhiduan Cai2, Zhaodong Han1, Yuxiang Liang1, Yangjia Zhuo1, Yong Luo1, Xuejin Zhu3, Yulin Deng2, Yixun Zhang1, Ren Liu2, Yuanfa Feng3, Jiarun Lai3, Rui Zhou1, Huijing Tan1, Weide Zhong1,2,3,4✉

1. Department of Urology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510180, China.
2. Guangdong Provincial Institute of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China.
3. Urology Key Laboratory of Guangdong Province, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, 510230, China.
4. Department of Urology, Huadu District People's Hospital, Southern Medical University, Guangzhou, Guangdong, 510800, China.
*These authors contributed equally to this work.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Zhang H, Liu S, Cai Z, Dong W, Ye J, Cai Z, Han Z, Liang Y, Zhuo Y, Luo Y, Zhu X, Deng Y, Zhang Y, Liu R, Feng Y, Lai J, Zhou R, Tan H, Zhong W. Down-regulation of ACACA suppresses the malignant progression of Prostate Cancer through inhibiting mitochondrial potential. J Cancer 2021; 12(1):232-243. doi:10.7150/jca.49560. Available from https://www.jcancer.org/v12p0232.htm

File import instruction


Background and aim: Silencing the expression of ACACA inhibits cell proliferation and induces apoptosis in prostate cancer LNCaP cells. However, the role of ACACA in other prostate cancer cells is not fully understood. Also, the effect of knocking down ACACA gene on mitochondria remains unclear. This study aimed to discover the specific role of ACACA gene in prostate cancer (PCa) DU145 and PC3 cells as well as its effects on mitochondrial potential.

Methods: The expression of ACACA gene was detected in human prostate cancer tissue microarrays and assessed in different clinical stages. Then, prostate cancer cell lines with low expression of ACACA were constructed to evaluate the changes in their cell cycle, proliferation, and metabolites. The effect of ACACA on tumor formation in vivo was analyzed. Also, mito-ATP production, mitochondrial staining, and mtDNA, nicotinamide adenine dinucleotide (NAD+/NADH), and reactive oxygen species (ROS) levels were detected.

Results: ACACA was expressed more strongly in prostate cancer tissues. The expression level of ACACA was higher in patients with advanced PCa than in patients with lower grades. The proliferation ability reduced in ACACA-knockdown cells. In in vivo tests, the tumor volume and weight were lower in the experimental group than in the control group. Mito-ATP production decreased significantly after ACACA suppression, mtDNA levels and MitoTracker staining decreased in the experimental group. The ratio of NAD+/NADH and ROS levels were upregulated in the experimental group.

Conclusion: Targeting ACACA gene and mitochondria might serve as a novel therapy for prostate cancer treatment.

Keywords: ACACA, Mitochondria, DU145, PC3, Prostate cancer