Fang Liu1, Li Chang2, Jinliang Hu3. 1. Department of Medical Laboratory, West China Second University Hospital, Sichuan University, Chengdu, Sichuan Province, China; Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Brith Defects of Ministry of Education, Chengdu, Sichuan Province, China. Electronic address: 44168160@qq.com. 2. Department of Medical Laboratory, West China Second University Hospital, Sichuan University, Chengdu, Sichuan Province, China; Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Brith Defects of Ministry of Education, Chengdu, Sichuan Province, China. Electronic address: 443526372@qq.com. 3. Institute of Health Policy & Hospital Management, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, Sichuan Province, China; West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan Province, China. Electronic address: hu_scsy@126.com.
Abstract
BACKGROUND: Cervical cancer cell function is influence by ER. Therefore, in this study, ER stress senser-ATF6, was selected for detailed research in cervical cancer. METHODS: ATF6 mRNA was assessed through RT-qPCR assays. Cell transfection was to regulate ATF6 and thereafter the differential ATF6 cancer cells were divided into two groups for further functional assays. Cell viabilities were analyzed by CCK-8 and migration by Scratch. RT-qPCR examined cell death biomarkers Caspas-3 and Bcl-2. 4-PBA was utilized to inhibit ER stress. After that, ATF6, viability, migration and apoptotic proteins were scrutinized after ER inhibition. Proteins signifying EMT, autophagy and MAPK signaling pathway were checked by western bolt. Last, we inactivated the MAPK signaling to investigate into the changes in cell functions. RESULTS: ATF6 presented higher expression in cervical cancer cells. Inhibited ATF6 could reduce cell viabilities and migration but promote apoptosis through suppressing Bcl-2 and increasing caspase-3. ER stress antagonist witnessed a drop in ATF6 expression, cell viability, migration and Bcl-2 but a rise in caspase-3 activation, suggesting apoptosis increase. Cell autophagy was hindered in CC cells. Knockdown of ATF6 promoted autophagy and restrained EMT and MAPK signaling pathway. Suppressed ERK1/2 obstructed cell viabilities, migration, EMT and autophagy but promoted apoptosis. CONCLUSION: ATF6 might promote cell growth, migration, autophagy through ER stress and MAPK signaling in cervical cancer in vitro, indicating a potential regulatory gene in cervical cancer. However, in-depth researches are requested to enrich the knowledge of ATF6 in cervical cancer in vivo and in clinical in the future.
BACKGROUND: Cervical cancer cell function is influence by ER. Therefore, in this study, ER stress senser-ATF6, was selected for detailed research in cervical cancer. METHODS:ATF6 mRNA was assessed through RT-qPCR assays. Cell transfection was to regulate ATF6 and thereafter the differential ATF6cancer cells were divided into two groups for further functional assays. Cell viabilities were analyzed by CCK-8 and migration by Scratch. RT-qPCR examined cell death biomarkers Caspas-3 and Bcl-2. 4-PBA was utilized to inhibit ER stress. After that, ATF6, viability, migration and apoptotic proteins were scrutinized after ER inhibition. Proteins signifying EMT, autophagy and MAPK signaling pathway were checked by western bolt. Last, we inactivated the MAPK signaling to investigate into the changes in cell functions. RESULTS:ATF6 presented higher expression in cervical cancer cells. Inhibited ATF6 could reduce cell viabilities and migration but promote apoptosis through suppressing Bcl-2 and increasing caspase-3. ER stress antagonist witnessed a drop in ATF6 expression, cell viability, migration and Bcl-2 but a rise in caspase-3 activation, suggesting apoptosis increase. Cell autophagy was hindered in CC cells. Knockdown of ATF6 promoted autophagy and restrained EMT and MAPK signaling pathway. Suppressed ERK1/2 obstructed cell viabilities, migration, EMT and autophagy but promoted apoptosis. CONCLUSION:ATF6 might promote cell growth, migration, autophagy through ER stress and MAPK signaling in cervical cancer in vitro, indicating a potential regulatory gene in cervical cancer. However, in-depth researches are requested to enrich the knowledge of ATF6 in cervical cancer in vivo and in clinical in the future.
Authors: Sze Wan Hung; Yiran Li; Xiaoyan Chen; Kai On Chu; Yiwei Zhao; Yingyu Liu; Xi Guo; Gene Chi-Wai Man; Chi Chiu Wang Journal: Front Pharmacol Date: 2022-07-04 Impact factor: 5.988