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动力蛋白轻链Tctex型3对卵巢癌生物学行为的影响

Effects of dynein light chain Tctex-type 3 on the biological behavior of ovarian cancer.

作者信息

Zhou Lulu, Ye Miaomiao, Xue Fang, Lu Ermei, Sun Lu-Zhe, Zhu Xueqiong

机构信息

Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325027, People's Republic of China.

Departments of Cell Systems & Anatomy, School of Medicine, University of Texas Health Science Center, San Antonio, TX, USA.

出版信息

Cancer Manag Res. 2019 Jul 1;11:5925-5938. doi: 10.2147/CMAR.S205158. eCollection 2019.

Abstract

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 invasion- and migration-related 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.

摘要

目的

研究动力蛋白轻链Tctex型3(DYNLT3)蛋白在卵巢上皮性病变中的表达情况,并探讨DYNLT3对卵巢癌生物学行为的影响及相关机制。

材料与方法

首先,采用免疫组织化学染色检测DYNLT3蛋白在卵巢上皮性病变中的表达,利用Kaplan-Meier plotter数据库评估DYNLT3 mRNA表达在卵巢癌患者中的预后价值。然后,分别通过定量实时聚合酶链反应和蛋白质免疫印迹法评估DYNLT3在IOSE80正常卵巢上皮细胞和SKOV3卵巢癌细胞中的mRNA和蛋白表达,分别采用CCK-8法、免疫荧光染色、流式细胞术、伤口愈合试验和Transwell侵袭试验研究DYNLT3过表达和低表达后SKOV3细胞的增殖、凋亡、迁移和侵袭情况。此外,通过蛋白质免疫印迹法检测细胞中增殖相关蛋白PCNA和Ki-67以及侵袭和迁移相关蛋白Ezrin、Fascin、MMP2和MMP9的表达。

结果

DYNLT3蛋白表达在卵巢上皮性病变进展过程中逐渐升高,且与卵巢癌的发生发展相关。DYNLT3 mRNA高表达与总体生存率和无进展生存率低相关,尤其是在浆液性卵巢癌患者中。此外,DYNLT3过表达促进SKOV3细胞增殖、侵袭和迁移。DYNLT3敲低试验也验证了相应结果。此外,DYNLT3促进细胞增殖,这与Ki-67表达有关。此外,DYNLT3通过调节Ezrin增强细胞侵袭和迁移,但不调节Fascin、MMP2或MMP9。

结论

DYNLT3可能通过调节Ki-67和Ezrin的蛋白表达促进细胞增殖、迁移和侵袭,从而对卵巢癌发挥促肿瘤作用。DYNLT3可能是卵巢癌潜在的预后预测指标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3824/6612992/f3bb77fb852b/CMAR-11-5925-g0001.jpg

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