Zhang Min, Li Qiong, Zhang Lu, Wang Yunjian, Wang Linxia, Li Qingjun, He Tao, Wan Baishun, Wang Xiaoqian
Department of Hepatobiliary Surgery, The Affiliated Cancer Hospital of Zhengzhou University, zhengzhou Henan 450008, China.
Nursing college, Xinxiang Medical University, Xinxiang Henan 453003, China.
Cell Mol Biol (Noisy-le-grand). 2018 Apr 30;64(5):73-79.
The Ras-association domain family (RASSF) proteins have been involved in many important biological processes. RASSF7 is recently reported to be up-regulated in several types of cancer. However, the function of RASSF7 remain unknown in human cancers. To explore the role of RASSF7 in hepatocellular carcinoma (HCC) cells proliferation and molecular mechanism. RASSF7 expression was examined using public database TCGA, qRT-PCR and Western blot. The correlation between RASSF7 and clinicopathological features was measured. Overexpression and silencing of RASSF7 were performed to measure the impact on HCC cell proliferation, cell cycle and apoptosis. Futhermore, the molecular mechanism of MEK1/2-ERK1/2 signaling pathway regulation by RASSF7 was explored. RASSF7 was significantly up-regulated in HCC tissues and cell lines, and correlated with AFP, poor tumor histology and T stage. Overexpression of RASSF7 promoted HCC cell proliferation, drived G1-S phase cell cycle transition and inhibited apoptosis. Knockdown of RASSF7 suppressed cell growth, induced G1-S phase cell cycle arrest and cell apoptosis. Furthermore, our findings also demonstrated that RASSF7 promoted HCC cell proliferation through activating MEK1/2-ERK1/2 signaling pathway. Taken together, this study provides a novel evidence for clinical significance of RASSF7 as a potential biomarker, and demonstrates that RASSF7- MEK1/2-ERK1/2 signaling pathway might be a novel pathway involved in HCC progression.
Ras 关联结构域家族(RASSF)蛋白参与了许多重要的生物学过程。最近有报道称 RASSF7 在几种癌症类型中表达上调。然而,RASSF7 在人类癌症中的功能仍不清楚。为了探究 RASSF7 在肝癌(HCC)细胞增殖中的作用及其分子机制,我们利用公共数据库 TCGA、qRT-PCR 和蛋白质免疫印迹法检测了 RASSF7 的表达情况。测定了 RASSF7 与临床病理特征之间的相关性。通过过表达和沉默 RASSF7 来检测其对 HCC 细胞增殖、细胞周期和凋亡的影响。此外,还探究了 RASSF7 调控 MEK1/2-ERK1/2 信号通路的分子机制。RASSF7 在 HCC 组织和细胞系中显著上调,且与甲胎蛋白、不良肿瘤组织学和 T 分期相关。RASSF7 的过表达促进了 HCC 细胞增殖,推动了 G1-S 期细胞周期转变并抑制了细胞凋亡。敲低 RASSF7 则抑制了细胞生长,诱导了 G1-S 期细胞周期阻滞和细胞凋亡。此外,我们的研究结果还表明,RASSF7 通过激活 MEK1/2-ERK1/2 信号通路促进 HCC 细胞增殖。综上所述,本研究为 RASSF7 作为潜在生物标志物的临床意义提供了新的证据,并表明 RASSF7-MEK1/2-ERK1/2 信号通路可能是一条参与 HCC 进展的新通路。