Bo Xiaobo, Chen Yusheng, Sheng Weizhong, Gong Yuda, Wang Haiyu, Gao Weidong, Zhang Bo
Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.
Oncol Lett. 2018 Mar;15(3):3630-3638. doi: 10.3892/ol.2018.7740. Epub 2018 Jan 8.
Gastric cancer is a major cause of cancer-associated mortality worldwide. The aberrant expression of microRNA (miRNA) is involved in tumorigenesis. Ras proteins transfer information from the extracellular environment to internal cellular compartments and are essential in numerous signal transduction pathways. To investigate the regulation, function and clinical significance of the miRNA377/Ras association domain family (RASSF) 8 signaling axis in gastric cancer, reverse transcription-quantitative polymerase chain reaction, immunohistochemistry, cell counting kit-8, western blotting, and Transwell assays were used. The results revealed that expression of RASSF8 was significantly upregulated in normal gastric tissues compared with gastric cancer, which was further confirmed by immunohistochemical analysis, and its expression level was increased in normal gastric cells compared with gastric cancer cell lines. However, the expression of miR-377 was significantly upregulated in gastric cancer compared with normal gastric tissues. In addition, RASSF8 overexpression in BGC-823 gastric cancer cells significantly inhibited the proliferation, apoptosis and invasive abilities of cells. Whereas miR-377 attenuated these effects due to downregulated RASSF8 expression by directly targeting its 3'-untranslated region. Furthermore, in the current study, miR-377 was not able to reverse the effects of RASSF8 overexpression on gastric cancer cells. Collectively, the RASSF8 gene may represent a novel molecular target involved in gastric cancer development and may be useful in targeted therapy of patients with gastric cancer.
胃癌是全球癌症相关死亡的主要原因。微小RNA（miRNA）的异常表达参与肿瘤发生。Ras蛋白将信息从细胞外环境传递到细胞内区室，在众多信号转导途径中起重要作用。为了研究miRNA377/ Ras关联结构域家族（RASSF）8信号轴在胃癌中的调控、功能及临床意义，采用了逆转录定量聚合酶链反应、免疫组织化学、细胞计数试剂盒-8、蛋白质印迹法和Transwell实验。结果显示，与胃癌组织相比，正常胃组织中RASSF8的表达显著上调，免疫组织化学分析进一步证实了这一点，并且与胃癌细胞系相比，正常胃细胞中其表达水平升高。然而，与正常胃组织相比，miR-377在胃癌中的表达显著上调。此外，在BGC-823胃癌细胞中过表达RASSF8可显著抑制细胞的增殖、凋亡和侵袭能力。而miR-377通过直接靶向RASSF8的3'-非翻译区下调其表达，从而减弱了这些作用。此外，在本研究中，miR-377无法逆转RASSF8过表达对胃癌细胞的影响。总的来说，RASSF8基因可能是参与胃癌发生发展的一个新的分子靶点，可能对胃癌患者的靶向治疗有用。
