TSPO is a novel biomarker for prognosis that regulates cell proliferation through influencing mitochondrial functions in HCC
Jia-Hao Pan,
Yin-Qian Kang,
Qiang Li,
Wei Xing,
Yong-Hua Chen,
Yan Yan,
De-Xing Luo,
Yue Qiu,
Yun-Fei Yuan,
Wei-An Zeng,
Dong-Tai Chen
Affiliations
Jia-Hao Pan
Department of Anesthesiology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
Yin-Qian Kang
Department of Anesthesiology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
Qiang Li
Department of Anesthesiology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
Wei Xing
Department of Anesthesiology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
Yong-Hua Chen
Department of Anesthesiology, Peking University Shenzhen Hospital, Shenzhen, China
Yan Yan
Department of Anesthesiology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; Department of Anesthesiology, Huizhou Municipal Central Hospital, Huizhou, China
De-Xing Luo
Department of Anesthesiology, Huizhou Municipal Central Hospital, Huizhou, China
Yue Qiu
Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
Yun-Fei Yuan
Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
Wei-An Zeng
Department of Anesthesiology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; Corresponding author.
Dong-Tai Chen
Department of Anesthesiology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; Corresponding author.
The disorder of mitochondrial functions plays a key role in oncogenesis. It is known that TSPO (18-kDa translocator protein) lies in a peculiar location at the interface between the mitochondria and the cytosol. TSPO is found in many types of tissues and is associated with multiple cellular processes, including apoptosis, cell proliferation and the regulation of mitochondria. However, the involvement of TSPO in hepatocellular carcinoma (HCC) remains unclear. In this study, we found that TSPO is upregulated in HCC tissue and is associated with poor differentiation and poor survival. Multivariate analyses showed that TSPO was an independent predictive factor for poor prognosis in HCC patients. For the first time, we provided evidence that TSPO knockdown suppressed HCC cell proliferation in vitro. Hence, TSPO knockdown-induced apoptosis by disturbing mitochondrial function by enhancing the formation of reactive oxygen species (ROS) and decreasing the mitochondrial membrane potential (ΔΨm). An assay exploring the underlying mechanism revealed that TSPO knockdown modulated apoptotic regulatory proteins by regulating the ERK signaling pathway. Through a functional assay and an in vivo mouse model, the anti-cancer effect of PK11195, a specific ligand of TSPO, on HCC was revealed. In summary, TSPO may potentially serve as a prognostic biomarker, and TSPO might be a potential therapeutic target for HCC.
