Li Chang, Li Xiaoping, Gao Shuohui, Li Chang, Ma Lianjun
Oncol Res. 2017 Aug 7;25(7):1169-1176. doi: 10.3727/096504017X14847395834985. Epub 2017 Jan 20.
Gastric cancer is the fourth most common type of cancer and the second highest leading cause of cancer-related deaths worldwide. It has already been established that miR-133a is involved in gastric cancer. In this study, we investigated the molecular mechanisms by which miR-133a inhibits the proliferation of gastric cancer cells. We analyzed the proliferative capacity of human gastric cancer cells SNU-1 using an MTT assay. Cell apoptosis was determined using flow cytometry. The expression levels of ERBB2, p-ERK1/2, and p-AKT in SNU-1 cells were determined using Western blot analysis. To confirm that ERBB2 is a direct target of miR-133a, a luciferase reporter assay was performed. Results showed that miR-133a overexpression inhibited SNU-1 cell proliferation and increased apoptosis. ERBB2 was a direct target of miR-133a, and it was negatively regulated by miR-133a. Interestingly, ERBB2 silencing has a similar impact to miR-133a overexpression, in that it significantly induced apoptosis and inhibited ERK and AKT activation. Our study showed that miR-133a inhibits the proliferation of gastric cancer cells by downregulating the expression of ERBB2 and its downstream signaling molecules p-ERK1/2 and p-AKT. Therefore, miR-133a might be used as a therapeutic target for treating gastric cancer.
胃癌是全球第四大常见癌症类型，也是癌症相关死亡的第二大主要原因。已有研究证实miR-133a与胃癌有关。在本研究中，我们探究了miR-133a抑制胃癌细胞增殖的分子机制。我们使用MTT法分析了人胃癌细胞SNU-1的增殖能力。通过流式细胞术测定细胞凋亡情况。使用蛋白质免疫印迹分析测定SNU-1细胞中ERBB2、p-ERK1/2和p-AKT的表达水平。为了证实ERBB2是miR-133a的直接靶点，进行了荧光素酶报告基因检测。结果显示，miR-133a过表达抑制了SNU-1细胞增殖并增加了细胞凋亡。ERBB2是miR-133a的直接靶点，且受到miR-133a的负调控。有趣的是，ERBB2沉默与miR-133a过表达具有相似的影响，即它显著诱导细胞凋亡并抑制ERK和AKT激活。我们的研究表明，miR-133a通过下调ERBB2及其下游信号分子p-ERK1/2和p-AKT的表达来抑制胃癌细胞增殖。因此，miR-133a可能用作治疗胃癌的治疗靶点。
