Activating transcription factor 6 regulated cell growth, migration and inhibiteds cell apoptosis and autophagy via MAPK pathway in cervical cancer. (June 2020)

• Record Type: Journal Article
• Authors: Liu, Fang; Chang, Li; Hu, Jinliang
• Is Part Of: Journal of reproductive immunology. Volume 139(2020)
• Publication Date: 2020-06
• Subjects: Activating transcription factor 6 -- MAPK pathway -- Cervical cancer -- ER stress; Reproduction -- Immunological aspects -- Periodicals; Immunology -- Periodicals; Allergy and Immunology -- Periodicals; Reproduction -- Periodicals; Reproduction -- Immunologie -- Périodiques; Immunologie -- Périodiques; Immunology; Reproduction -- Immunological aspects; Periodicals; Electronic journals; Electronic journals; 615.766
• DOI: 10.1016/j.jri.2020.103120
• Languages: English
• ISSNs: 0165-0378

Abstract

Highlights: Silenced ATF6 hindered cell viability, migration, MAPK signaling activation but promoted apoptosis and autophagy in CC. 4-PBA was utilized and induced a fall in ATF6, cell viability and migration and an increase of cell apoptosis and autophagy. Inactivated MAPK signaling led to a decrease in cell viability, migration and an increase in cell autophagy and apoptosis. 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.