Cmar_a_205158 5925..5938

Lulu Zhou Miaomiao Ye Fang Xue Ermei Lu Lu-Zhe Sun Xueqiong Zhu 1Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325027, People’s Republic of China; 2Departments of Cell Systems & Anatomy, School of Medicine, University of Texas Health Science Center, San Antonio, TX, USA Objective: To investigate dynein light chain Tctex-type 3 (DYNLT3) protein expression in ovarian epithelial lesions and explore the effects and related mechanisms of DYNLT3 in terms of the biological behavior of ovarian cancer. Materials and methods: Initially, expression of the DYNLT3 protein in ovarian epithelial lesions was detected by immunohistochemical staining, and the prognostic value of DYNLT3 mRNA expression in ovarian cancer patients was assessed using the Kaplan-Meier plotter database. Then, the mRNA and protein expression of DYNLT3 in IOSE80 normal ovarian epithelial cells and SKOV3 ovarian cancer cells was evaluated by quantitative real-time polymerase chain reaction and Western blotting respectively, and the proliferation, apoptosis, migration and invasion of SKOV3 cells after DYNLT3 over-expression and under-expression were investigated by CCK-8 assays and immunofluorescence staining, flow cytometry, wound healing assays and Transwell invasion assays, respectively. Furthermore, the expression of the proliferation-related proteins PCNA and Ki-67 and the invasionand migrationrelated proteins Ezrin, Fascin, MMP2 and MMP9 in cells was examined by Western blotting. Results: The protein expression of DYNLT3 gradually increased during the progression of ovarian epithelial lesions, and was related to the development of ovarian cancer. High expression of DYNLT3 mRNA was related to poor overall survival and progression free survival, especially in serous ovarian cancer patients. In addition, overexpression of DYNLT3 promoted SKOV3 cell proliferation, invasion and migration. The corresponding results were also verified by a DYNLT3 knockdown assay. Moreover, DYNLT3 increased cell proliferation, which was related to Ki-67 expression. Besides, DYNLT3 enhanced cell invasion and migration through regulating Ezrin, but not Fascin, MMP2 or MMP9. Conclusion: DYNLT3 exerts pro-tumoral effects on ovarian cancer through promoting cell proliferation, migration and invasion, possibly via regulating the protein expression of Ki-67 and Ezrin. DYNLT3 may be a potential prognostic predictor in ovarian cancer.