CREBRF promotes the proliferation of human gastric cancer cells via the AKT signaling pathway
CREBRF promotes the proliferation of human gastric cancer cells via the AKT signaling pathway
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CREBRF通过AKT信号通路促进人胃癌细胞增殖
DOI：
10.14715/cmb/2018.64.5.6
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发表时间：
2018-01-01
影响因子：
1.6
通讯作者：
Huang, Chen
中科院分区：
文献类型：
--
作者：
Han, Jiming;Zhang, Lu;Huang, Chen
胃癌（Gastric cancer，GC）是世界上最常见的恶性肿瘤之一，其发病机制尚不清楚。本研究探讨CREB 3调节因子（CREBRF）在人胃癌中的作用及其分子机制。我们发现CREBRF在原发性胃癌组织中高表达，其表达水平与胃癌的临床病理特征有关。CREBRF基因沉默可通过调节Cyclin A、Cyclin D1和CDK 2的表达，抑制胃癌细胞增殖，使胃癌细胞周期阻滞于G1/G 0期，进入S期。此外，结果表明，敲低CREBRF抑制AKT信号通路的激活。我们进一步发现，激活AKT挽救了CREBRF沉默对细胞生长的影响，并与SC 79（AKT激活剂）一起驱动细胞重新进入细胞周期的S期。综上所述，我们的研究表明CREBRF可能通过激活AKT信号通路促进GC细胞增殖，并诱导G1-S期转变。提示CREBRF是一种新的癌基因，可能成为胃癌治疗的潜在靶点。
Gastric cancer (GC) is one of the most common malignant cancer around the world, however the mechanisms is still unclear. In the present study, we investigated the function of CREB3 regulatory factor (CREBRF) in human GC and explored its relevant molecular mechanism. We found that CREBRF was highly expressed in primary GC tissues and the expression level was associated with the clinicopathologic characteristics of GC. CREBRF silencing inhibited GC cell proliferation and induced G1/G0 to S phase cell cycle arrest through regulating Cyclin A, Cyclin D1 and CDK2 expressions. Furthermore, the results showed that knockdown of CREBRF suppressed the activation of AKT signaling pathway. We further discovered that activating of AKT rescued the effect of CREBRF silencing on cell growth and drove cell re-enter into the S phase of the cell cycle with SC79 (a AKT activator). Taken together, our study demonstrated that CREBRF might promote GC cell proliferation and induce G1-S phase transition through activating AKT signaling pathway. These findings suggest that CREBRF acts as a novel oncogene and may be a potential therapeutic target in therapy of GC.