Chun-Hsien Wu1,2,3, Pei-Fang Hsieh1,4, Yen-Hsi Lee2,5, Wade Wei-Ting Kuo1,2, Richard Chen-Yu Wu1,6, Yung-Yao Lin1,6, Chih-Hsin Hung2, Ming-Lin Hsieh7, See-Tong Pang7, Yu-Lin Yang4,8, Victor C Lin9,6. 1. Department of Urology, E-Da Hospital, Kaohsiung, Taiwan, R.O.C. 2. Department of Chemical Engineering and Institute of Biotechnology and Chemical Engineering, I-Shou University, Kaohsiung, Taiwan, R.O.C. 3. Department of Nursing, I-Shou University, Kaohsiung, Taiwan, R.O.C. 4. Graduate Institute of Medical Laboratory Science and Biotechnology, Chung-Hwa University of Medical Technology, Tainan, Taiwan, R.O.C. 5. Department of Urology, E-Da Cancer Hospital, Kaohsiung, Taiwan, R.O.C. 6. School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan, R.O.C. 7. Chang Gung Memorial Hospital Linkou and Chang Gung University, Taoyuan, Taiwan, R.O.C. 8. Graduate Institute of Biomedical Science, Chung-Hwa University of Medical Technology, Tainan, Taiwan, R.O.C. 9. Department of Urology, E-Da Hospital, Kaohsiung, Taiwan, R.O.C.; victorlin0098@gmail.com.
Abstract
BACKGROUND/AIM: The role of nuclear respiratory factor 1 (NRF1) on the prostate cancer progression is controversial. We aimed to investigate the effect of NRF1 overexpression on the metastasis potential of PC3 prostate cancer cells and the associated molecular mechanisms. MATERIALS AND METHODS: Cell survival, migration capacity, mitochondrial biogenesis, the expression of TGF-β signaling and EMT markers were examined after overexpression and silencing of NRF1 in PC3 cells. RESULTS: We found that NRF1-overexpressing cells exhibited a decreased cell viability and proliferation ability as well as a reduced migration capacity compared to control cells. Moreover, ectopic expression of NRF1 increased the mitochondrial biogenesis and inhibited the EMT characteristics, including a decrease in the mesenchymal marker, α-SMA and an increase in the epithelial cell marker, E-cadherin. We also demonstrated that overexpression of NRF1 suppressed the expression of TGF-β signaling in PC3 cells. As expected, silencing of NRF1 reversed the abovementioned effects. CONCLUSION: This study demonstrated that upregulation of NRF1 holds the potential to inhibit the metastasis of prostate cancer, possibly through an elevation of mitochondrial biogenesis and the subsequent repression of TGF-β-associated EMT. Therapeutic avenues that increase NRF1 expression may serve as an adjunct to conventional treatments of prostate cancer. Copyright
BACKGROUND/AIM: The role of nuclear respiratory factor 1 (NRF1) on the prostate cancer progression is controversial. We aimed to investigate the effect of NRF1 overexpression on the metastasis potential of PC3 prostate cancer cells and the associated molecular mechanisms. MATERIALS AND METHODS: Cell survival, migration capacity, mitochondrial biogenesis, the expression of TGF-β signaling and EMT markers were examined after overexpression and silencing of NRF1 in PC3 cells. RESULTS: We found that NRF1-overexpressing cells exhibited a decreased cell viability and proliferation ability as well as a reduced migration capacity compared to control cells. Moreover, ectopic expression of NRF1 increased the mitochondrial biogenesis and inhibited the EMT characteristics, including a decrease in the mesenchymal marker, α-SMA and an increase in the epithelial cell marker, E-cadherin. We also demonstrated that overexpression of NRF1 suppressed the expression of TGF-β signaling in PC3 cells. As expected, silencing of NRF1 reversed the abovementioned effects. CONCLUSION: This study demonstrated that upregulation of NRF1 holds the potential to inhibit the metastasis of prostate cancer, possibly through an elevation of mitochondrial biogenesis and the subsequent repression of TGF-β-associated EMT. Therapeutic avenues that increase NRF1 expression may serve as an adjunct to conventional treatments of prostate cancer. Copyright
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