Xie Gengchen, Li Wei, Li Ruidong, Wu Ke, Zhao Ende, Zhang Yu, Zhang Peng, Shi Liang, Wang Di, Yin Yuping, Deng Rui, Tao Kaixiong
Department of Gastrointestinal Surgery of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China.
Department of Radiology of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China.
PLoS One. 2017 Jan 5;12(1):e0168822. doi: 10.1371/journal.pone.0168822. eCollection 2017.
The most common cause of gastric cancer is infection with helicobacter pylori (HP), but the associated molecular mechanism is not well understood. In the present study, we found a marked increase in the expression of B7-H1, a member of the B7 co-stimulatory family of molecules that bind to programmed death-1 (PD-1) and play a critical immunoregulatory role in the cell-mediated immune response, in HP-positive gastric cancer tissue. Infection of cultured gastric cancer cells with HP promoted B7-H1 expression and inhibited miR-152 and miR-200b expression. We further demonstrated that these two miRNAs targeted B7-H1 mRNA and suppressed B7-H1 expression in gastric cancer cells. Finally, B7-H1 expression was found to correlate with miR-152 and miR-200b levels in gastric tumor tissues from human patients. Our findings suggest a novel mechanism by which HP infection promotes gastric cancer and also suggest potential targets, i.e., miR-152 and miR-200b, for the prevention and treatment of gastric cancer.
胃癌最常见的病因是幽门螺杆菌(HP)感染,但其相关分子机制尚未完全明确。在本研究中,我们发现B7-H1(一种B7共刺激分子家族成员,可与程序性死亡-1(PD-1)结合并在细胞介导的免疫反应中发挥关键免疫调节作用)在HP阳性胃癌组织中的表达显著增加。用HP感染培养的胃癌细胞可促进B7-H1表达,并抑制miR-152和miR-200b表达。我们进一步证明,这两种miRNA靶向B7-H1 mRNA并抑制胃癌细胞中B7-H1的表达。最后,发现B7-H1表达与人胃癌组织中miR-152和miR-200b水平相关。我们的研究结果提示了一种HP感染促进胃癌发生的新机制,也提示了预防和治疗胃癌的潜在靶点,即miR-152和miR-200b。