title: MiR-191 inhibits TNF-α induced apoptosis of ovarian endometriosis and endometrioid carcinoma cells by targeting DAPK1.
abstract: Emerging evidence showed that miRNA dysregulation is involved in the development of endometriosis and may contribute to pathological process of endometriosis associated ovarian cancer (EAOC). miR-191 is one of the most differentially expressed miRNAs in pairwise comparisons among healthy controls, endometriosis, and EAOC patients. However, its regulative network in endometriosis and EAOC are still not clear. This study explored the role of miR-191 in TNF-α induced cell death in ovarian endometriosis and endometrioid carcinoma cells. Based on tissues samples collected from healthy controls, endometriosis, and EAOC patients, this study verified significantly higher expression of miR-191 in endometriosis and endometrioid cancer. Interestingly, we also observed inverse expression trend between miR-191 and DAPK1, a positive mediator of programmed cell death. By conducting luciferase assay, we confirmed miR-191 can directly target DAPK1 and regulate its expression. Functionally, we also found DAPK1 can promote TNF-α induced cell death. DAPK1 knockdown in endometriosis CRL-7566 cells can weaken its response to TNF-α induced cell death, while its overexpression in endometrioid cancer cells CRL-11731 enhanced the response. These functions of DAPK1 can be directly modulated by miR-191. Therefore, the miR-191-DAPK1 axis may play an important role modulating the response of ovarian endometriosis and endometrioid carcinoma cells to death-inducers and might contribute malignant transformation of endometriosis.
authors.affiliation: Medical School of Jinan University #601, Huangpu Avenue West, Guangzhou, China ; Guangzhou University of Chinese Medicine Guangzhou, #12, Airport Road, Guangzhou 510405, China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Tian
authors.affiliation: The First Affiliated Hospital of Guangzhou University of Chinese Medicine #16, Airport Road, Guangzhou 510405, China.
authors.forename: Limian
authors.initials: L
authors.lastname: Xu
authors.affiliation: The First Affiliated Hospital of Guangzhou Medical University #151, Yanjiang Road, Guangzhou, 510120, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000187:drug effects*; D018269:Carcinoma, Endometrioid / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D064550:Death-Associated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D016889:Endometrial Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D004715:Endometriosis / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: C546177:MIRN191 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C579096:DAPK1 protein, human; D064550:Death-Associated Protein Kinases
keywords: DAPK1; EAOC; endometriosis; miR-191