Ninio-Many Lihi, Grossman Hadas, Levi Mattan, Zilber Sofia, Tsarfaty Ilan, Shomron Noam, Tuvar Anna, Chuderland Dana, Stemmer Salomon M, Ben-Aharon Irit, Shalgi Ruth
Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel-Aviv University, Israel.
This work was performed in partial fulfillment of the requirements for a Ph.D. degree of Lihi Ninio-Many, Sackler Faculty of Medicine, Tel Aviv University, Israel.
Oncoscience. 2014 Apr 30;1(4):250-261. doi: 10.18632/oncoscience.30. eCollection 2014.
Fyn kinase is implicated in prostate cancer. We illustrate the role of miR-125a-3p in cellular pathways accounted for motility and migration of prostate cancer cells, probably through its regulation on Fyn expression and Fyn-downstream proteins. Prostate cancer PC3 cells were transiently transfected with empty miR-Vec (control) or with miR-125a-3p. Overexpression of miR-125a-3p reduced migration of PC3 cells and increased apoptosis. Live cell confocal imaging indicated that overexpression of miR-125a-3p reduced the cells' track speed and length and impaired phenotype. Fyn, FAK and paxillin, displayed reduced activity following miR-125a-3p overexpression. Accordingly, actin rearrangement and cells' protrusion formation were impaired. An inverse correlation between miR-125a-3p and Gleason score was observed in human prostate cancer tissues. Our study demonstrated that miR-125a-3p may regulate migration of prostate cancer cells.
Fyn激酶与前列腺癌有关。我们阐述了miR-125a-3p在前列腺癌细胞运动和迁移相关细胞通路中的作用,这可能是通过其对Fyn表达及Fyn下游蛋白的调控来实现的。前列腺癌PC3细胞分别用空的miR-Vec(对照)或miR-125a-3p进行瞬时转染。miR-125a-3p的过表达降低了PC3细胞的迁移能力并增加了细胞凋亡。活细胞共聚焦成像显示,miR-125a-3p的过表达降低了细胞的轨迹速度和长度,并损害了细胞表型。miR-125a-3p过表达后,Fyn、FAK和桩蛋白的活性降低。相应地,肌动蛋白重排和细胞突起形成也受到损害。在人类前列腺癌组织中观察到miR-125a-3p与Gleason评分呈负相关。我们的研究表明,miR-125a-3p可能调控前列腺癌细胞的迁移。