Zhang J, Tong D D, Xue M, Jiang Q Y, Wang X F, Yang P B, Ni L, Zhao L Y, Huang C
Department of Cell Biology and Genetics/Key Laboratory of Environment and Genes Related to Diseases, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710049, Shaanxi Province, China.
Department of Human Anatomy and Histoembryology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710049, Shaanxi Province, China.
Cell Mol Biol (Noisy-le-grand). 2017 Sep 30;63(9):18-23. doi: 10.14715/cmb/2017.63.9.4.
Gastric cancer (GC) is the second leading cause of cancer-related deaths worldwide, but the mechanisms remain unknown. Here we report that family with sequence similarity 196 member B (FAM196B) is highly expressed in primary GC tissues and the expression level is correlated with the clinicopathologic characteristics of GC. In this experiment, knockdown of FAM196B suppressed GC cell proliferation and induced G1/G0 to S phase cell cycle arrest by regulating Cyclin D1, Cyclin A and CDK2 expressions. Furthermore, we investigated the molecular mechanism of FAM196B action in GC. The results showed that knockdown of FAM196B inhibited the activation of AKT signaling pathway. We further revealed that activating of AKT rescued the effect of FAM196B knockdown on cell proliferation and drove cell re-enter into the S phase of the cell cycle with SC79 (a AKT activator). Our findings demonstrated that FAM196B may promote GC cell proliferation by activating AKT signaling pathway. Taken together, this study provides a new evidence that FAM196B functions as a novel oncogene and could be a potential therapeutic target in therapy of GC.
胃癌(GC)是全球癌症相关死亡的第二大主要原因,但其机制尚不清楚。在此我们报告,序列相似性家族196成员B(FAM196B)在原发性胃癌组织中高表达,且表达水平与胃癌的临床病理特征相关。在本实验中,FAM196B的敲低抑制了胃癌细胞增殖,并通过调节细胞周期蛋白D1、细胞周期蛋白A和细胞周期蛋白依赖性激酶2(CDK2)的表达诱导G1/G0期至S期的细胞周期阻滞。此外,我们研究了FAM196B在胃癌中的作用分子机制。结果显示,FAM196B的敲低抑制了AKT信号通路的激活。我们进一步发现,使用SC79(一种AKT激活剂)激活AKT可挽救FAM196B敲低对细胞增殖的影响,并促使细胞重新进入细胞周期的S期。我们的研究结果表明,FAM196B可能通过激活AKT信号通路促进胃癌细胞增殖。综上所述,本研究提供了新的证据,表明FAM196B作为一种新的癌基因发挥作用,并且可能是胃癌治疗中的一个潜在治疗靶点。