2. Academic Validation
  3. Nuclear genome-derived circular RNA circPUM1 localizes in mitochondria and regulates oxidative phosphorylation in esophageal squamous cell carcinoma

Nuclear genome-derived circular RNA circPUM1 localizes in mitochondria and regulates oxidative phosphorylation in esophageal squamous cell carcinoma

  • Signal Transduct Target Ther. 2022 Feb 14;7(1):40. doi: 10.1038/s41392-021-00865-0.
Wei Gong  # 1,  Jiancheng Xu  # 2,  Yan Wang 1,  Qingjie Min 1,  Xu Chen 1,  Weimin Zhang 1,  Jie Chen 1,  Qimin Zhan 3 4 5 6
Affiliations

Affiliations

  • 1 Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Molecular Oncology, Peking University Cancer Hospital & Institute, 100142, Beijing, China.
  • 2 Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, 100191, Beijing, China.
  • 3 Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Molecular Oncology, Peking University Cancer Hospital & Institute, 100142, Beijing, China. zhanqimin@bjmu.edu.cn.
  • 4 Peking University International Cancer Institute, 100191, Beijing, China. zhanqimin@bjmu.edu.cn.
  • 5 Shenzhen Bay Laboratory, Shenzhen, 518132, China. zhanqimin@bjmu.edu.cn.
  • 6 Research Unit of Molecular Cancer Research, Chinese Academy of Medical Sciences, 100021, Beijing, China. zhanqimin@bjmu.edu.cn.
  • # Contributed equally.
PMID: 35153295 DOI: 10.1038/s41392-021-00865-0
Abstract

Circular RNAs (circRNAs) were shown to play an important role in the occurrence and progression of tumors. However, the functions of nuclear genome-derived circRNAs localized in mitochondria of tumor cells remain largely elusive. Here, we report that circPUM1, a circular RNA derived from back-splicing of pre-mRNAs of nuclear genome PUM1, localizes in mitochondria. The expression level of circPUM1 is positively correlated with HIF1α accumulation under CoCl2-induced intracellular hypoxic-like condition in esophageal squamous cell carcinoma (ESCC) cell lines. Importantly, circPUM1 acts as a scaffold for the interaction between UQCRC1 and UQCRC2 in ESCC cell lines. Knock-down of circPUM1 would result in lower intracellular oxygen concentration, downregulated Oxidative Phosphorylation, decrease of mitochondrial membrane potential, increase of ROS generation and shrinking of mitochondria, respectively. CircPUM1 depletion induces dysfunction of the mitochondrial complex III and the cleavage of caspase3 spontaneously. Interestingly, disruption of circPUM1 led to Pyroptosis that initiates the cell death of ESCC cell lines. Therefore, we conclude that circPUM1 plays a critical role in maintaining the stability of mitochondrial complex III to enhance Oxidative Phosphorylation for ATP production of ESCC cells and moreover propose that ESCC cells exploit circPUM1 during cell adaptation.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z