Li Yuanyuan, Cui Nan, Zheng Peng-Sheng, Yang Wen-Ting
Department of Reproductive Medicine, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China.
Section of Cancer Stem Cell Research, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education of The People's Republic of China, Xi'an, People's Republic of China.
Oncotarget. 2017 Jul 25;8(30):49238-49252. doi: 10.18632/oncotarget.17493.
Bone marrow X-linked kinase (BMX, also known as Etk) has been reported to be involved in cell proliferation, differentiation, apoptosis, migration and invasion in several types of tumors, but its role in cervical carcinoma remains poorly understood. In this study, we showed that BMX expression exhibits a gradually increasing trend from normal cervical tissue to cervical cancer in situ and then to invasive cervical cancer tissue. Through BMX-IN-1, a potent and irreversible BMX kinase inhibitor, inhibited the expression of BMX, the cell proliferation was significantly decreased. Knockdown of BMX in HeLa and SiHa cervical cancer cell lines using two different silencing technologies, TALEN and shRNA, inhibited cell growth in vitro and suppressed xenograft tumor formation in vivo, whereas overexpression of BMX in the cell line C-33A significantly increased cell proliferation. Furthermore, a mechanism study showed that silencing BMX blocked cell cycle transit from G0/G1 to S or G2/M phase, and knockdown of BMX inhibited the expression of p-AKT and p-STAT3. These results suggested that BMX can promote cell proliferation through PI3K/AKT/mTOR and STAT3 signaling pathways in cervical cancer cells.
据报道，骨髓X连锁激酶（BMX，也称为Etk）参与多种肿瘤的细胞增殖、分化、凋亡、迁移和侵袭，但其在宫颈癌中的作用仍知之甚少。在本研究中，我们发现BMX的表达从正常宫颈组织到宫颈原位癌再到浸润性宫颈癌组织呈逐渐上升趋势。通过使用强效不可逆的BMX激酶抑制剂BMX-IN-1抑制BMX的表达，细胞增殖显著降低。使用TALEN和shRNA这两种不同的沉默技术在HeLa和SiHa宫颈癌细胞系中敲低BMX，可抑制体外细胞生长并抑制体内异种移植肿瘤形成，而在C-33A细胞系中过表达BMX则显著增加细胞增殖。此外，机制研究表明，沉默BMX可阻断细胞周期从G0/G1期向S期或G2/M期的转变，敲低BMX可抑制p-AKT和p-STAT3的表达。这些结果表明，BMX可通过PI3K/AKT/mTOR和STAT3信号通路促进宫颈癌细胞增殖。
