Knockdown of heat shock protein family D member 1 (HSPD1) promotes proliferation and migration of ovarian cancer cells via disrupting the stability of mitochondrial 3-oxoacyl-ACP synthase (OXSM).

Apr 24, 2023

Experts: Yaoyun Duan,Juan Yu,Miaojuan Chen,Qinsheng Lu,Fen Ning,Xiaowen Gan,Hanbo Liu,Yixin Ye,Shenjiao Lu,Gendie E Lash

Heat shock protein 60 (HSP60) is essential for the folding and assembly of newly imported proteins to the mitochondria. HSP60 is overexpressed in most types of cancer, but its association with ovarian cancer is still in dispute. SKOV3 and OVCAR3 were used as experimental models after comparing the expression level of mitochondrial HSP60 in a normal human ovarian epithelial cell line and four ovarian cancer cell lines.
Low HSPD1 (Heat Shock Protein Family D (HSP60) Member 1) expression was associated with unfavorable prognosis in ovarian cancer patients. Knockdown of HSPD1 significantly promoted the proliferation and migration of ovarian cancer cells. The differentially expressed proteins after HSPD1 knockdown were enriched in the lipoic acid (LA) biosynthesis and metabolism pathway, in which mitochondrial 3-oxoacyl-ACP synthase (OXSM) was the most downregulated protein and responsible for lipoic acid synthesis. HSP60 interacted with OXSM and overexpression of OXSM or LA treatment could reverse proliferation promotion mediated by HSPD1 knockdown.
HSP60 interacted with OXSM and maintained its stability. Knockdown of HSPD1 could promote the proliferation and migration of SKOV3 and OVCAR3 via lowering the protein level of OXSM and LA synthesis.

© 2023. The Author(s).

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ABOUT THE EXPERTS

Yaoyun Duan,Juan Yu,Miaojuan Chen,Qinsheng Lu,Fen Ning,Xiaowen Gan,Hanbo Liu,Yixin Ye,Shenjiao Lu,Gendie E Lash

Yaoyun Duan

Division of Uterine Vascular Biology, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, 510623, Guangzhou, China.

Juan Yu

Division of Uterine Vascular Biology, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, 510623, Guangzhou, China.

Miaojuan Chen

Division of Uterine Vascular Biology, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, 510623, Guangzhou, China.

Qinsheng Lu

Division of Uterine Vascular Biology, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, 510623, Guangzhou, China.

Fen Ning

Division of Uterine Vascular Biology, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, 510623, Guangzhou, China.

Xiaowen Gan

Division of Uterine Vascular Biology, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, 510623, Guangzhou, China.

Hanbo Liu

School of Medicine, South China University of Technology, Guangzhou, China.

Yixin Ye

School of Medicine, South China University of Technology, Guangzhou, China.

Shenjiao Lu

Division of Uterine Vascular Biology, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, 510623, Guangzhou, China.

Gendie E Lash

Division of Uterine Vascular Biology, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, 510623, Guangzhou, China. gendie.lash@hotmail.com.