FAM196B acts as oncogene and promotes proliferation of gastric cancer cells through AKT signaling pathway
FAM196B acts as oncogene and promotes proliferation of gastric cancer cells through AKT signaling pathway
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FAM196B作为癌基因通过AKT信号通路促进胃癌细胞增殖
DOI：
10.14715/cmb/2017.63.9.4
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发表时间：
2017-01-01
影响因子：
1.6
通讯作者：
Huang, C.
中科院分区：
文献类型：
--
作者：
Zhang, J.;Tong, D. D.;Huang, C.
胃癌（GC）是全球癌症相关死亡的第二大原因，但其机制尚不清楚。本文报道序列相似的家族196成员B （FAM196B）在胃癌原发组织中高表达，其表达水平与胃癌的临床病理特征相关。在本实验中，FAM196B基因的下调通过调节Cyclin D1、Cyclin A和CDK2的表达，抑制GC细胞增殖，诱导G1/G0至S期细胞周期阻滞。进一步探讨了FAM196B在GC中作用的分子机制。结果表明，FAM196B基因敲低可抑制AKT信号通路的激活。我们进一步发现，AKT的激活可以挽救FAM196B敲低对细胞增殖的影响，并通过SC79 （AKT激活剂）驱动细胞重新进入细胞周期的S期。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，本研究为FAM196B作为一种新型癌基因的功能提供了新的证据，并可能成为胃癌治疗的潜在靶点。
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.