Sun Weibo, Cang Shundong, Lv Xiaodong, Wang Ping, Lin Quande, Zhang Qing, Yan Zechen, Liu Zhongyang, Song Yongping
Henan Key Lab of Cancer Stem Cells, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou University Zhengzhou, Henan, China.
Department of Oncology, People's Hospital of Zhengzhou University, The Henan Province People's Hospital Zhengzhou, Henan, China.
Int J Clin Exp Pathol. 2017 Nov 1;10(11):10892-10900. eCollection 2017.
Breast cancer was a malignant tumor seriously threatening the life of women in the world. But the prognosis of breast cancer patients was not so satisfactory due to the limited effective therapeutics. The heterogeneity decided that more than one gene or one signaling pathway was responsible for the initiation or progression of breast cancer. DDX51 gene was a member of RNA helicases family in charge of regulation of RNA metabolism. And DDX51 gene was shown to promote proliferation in NSCLC. But we firstly reported the abundant expression of DDX51 gene in both the breast cancer tissues and cell lines in this study. And DDX51 expression was shown to be associated with TNM stage and prognosis in breast cancer patients. When DDX51 was successfully knocked down, either proliferation or DNA synthesis of MCF-7 cells was inhibited. But the ability of migration and invasion of MCF-7 cells was not affected by DDX51 gene. Furthermore, DDX51 knockdown was accompanied by inhibition of Wnt/β-catenin signaling because expression of critical members such as β-catenin, cyclin D1, TCF/LEF, and DKK1 were all affected. Therefore, this study proved that DDX51 gene promoted proliferation in MCF-7 cells by regulating Wnt/β-catenin signaling pathway and showed clinical significance in breast cancer. This study provides us a new promising hope for treatment of patients with breast cancer.
乳腺癌是一种严重威胁全球女性生命的恶性肿瘤。但由于有效治疗手段有限，乳腺癌患者的预后并不理想。其异质性决定了不止一个基因或一条信号通路参与乳腺癌的发生或发展。DDX51基因是RNA解旋酶家族的成员之一，负责调控RNA代谢。已有研究表明DDX51基因可促进非小细胞肺癌的增殖。但在本研究中，我们首次报道了DDX51基因在乳腺癌组织和细胞系中均有高表达。并且DDX51的表达与乳腺癌患者的TNM分期及预后相关。当DDX51被成功敲低后，MCF-7细胞的增殖或DNA合成均受到抑制。但DDX51基因并未影响MCF-7细胞的迁移和侵袭能力。此外，DDX51基因敲低伴随着Wnt/β-连环蛋白信号通路的抑制，因为β-连环蛋白、细胞周期蛋白D1、TCF/LEF和DKK1等关键成员的表达均受到影响。因此，本研究证明DDX51基因通过调控Wnt/β-连环蛋白信号通路促进MCF-7细胞增殖，并在乳腺癌中具有临床意义。本研究为乳腺癌患者的治疗提供了新的希望。
