Xu Weibo, Chang Junkai, Liu Guangchao, Du Xinyi, Li Xiaodong
Department of Urology, Huaihe Hospital of Henan University, Kaifeng 475000, Henan Province, China.
Antibody Drug Engineering Laboratory of Henan Province, Kaifeng 475000, Henan Province, China.
Biomed Pharmacother. 2017 Mar;87:471-475. doi: 10.1016/j.biopha.2016.12.120. Epub 2017 Jan 6.
Fork-head box R2 (FOXR2), a member of FOX protein family, was reported to play important roles in the development and progression of cancers. However, the expression and function of FOXR2 in prostate cancer remain unclear. In this study, we investigated the role of FOXR2 in prostate cancer and cancer progression including the molecular mechanism that drives FOXR2-mediated oncogenesis. Our results showed that FOXR2 was overexpressed in prostate cancer cell lines. The in vitro experiments demonstrated that knockdown of FOXR2 significantly repressed the proliferation, migration and invasiveness of prostate cancer cells. Furthermore, the in vivo experiments indicated that knockdown of FOXR2 significantly attenuated prostate cancer growth. Finally, knockdown of FOXR2 significantly down-regulated the protein expression levels of β-catenin, cyclinD1 and c-Myc in DU-145 cells. Taken together, our results demonstrated for the first time that FOXR2 plays a critical role in cell proliferation and invasion, at least in part, through inhibiting the Wnt/β-catenin signaling pathway during prostate cancer progression. Thus, FOXR2 may be an attractive therapeutic target for the treatment of prostate cancer.
叉头框R2(FOXR2)是FOX蛋白家族的一员,据报道在癌症的发生和发展中发挥重要作用。然而,FOXR2在前列腺癌中的表达和功能仍不清楚。在本研究中,我们研究了FOXR2在前列腺癌及其进展中的作用,包括驱动FOXR2介导的肿瘤发生的分子机制。我们的结果表明,FOXR2在前列腺癌细胞系中过表达。体外实验表明,敲低FOXR2可显著抑制前列腺癌细胞的增殖、迁移和侵袭。此外,体内实验表明,敲低FOXR2可显著减弱前列腺癌的生长。最后,敲低FOXR2可显著下调DU-145细胞中β-连环蛋白、细胞周期蛋白D1和c-Myc的蛋白表达水平。综上所述,我们的结果首次证明,FOXR2在前列腺癌进展过程中至少部分通过抑制Wnt/β-连环蛋白信号通路,在细胞增殖和侵袭中起关键作用。因此,FOXR2可能是治疗前列腺癌的一个有吸引力的治疗靶点。