Wang Qingqing, He Yuan, Kan Weiqiong, Li Fucai, Ji Xiangjun, Wu Xuewen, Wang Xinyue, Zhang Yue, Chen Jinlian
Department of Gastroenterology, Fengxian Hospital, Anhui University of Science and Technology Shanghai 201499, P. R. China.
Department of Gastroenterology, Fengxian Hospital, Southern Medical University Shanghai 201499, P. R. China.
Am J Transl Res. 2019 Aug 15;11(8):4895-4908. eCollection 2019.
Krüppel-like factor 2 (KLF2) is a member of the zinc finger family, which is considered a potential tumor suppressor gene due to its reduced expression in gastric cancer. MicroRNAs (miRNAs) are a class of short non-coding single-stranded RNAs that are closely related to the development of gastric cancer. The purpose of this study was to investigate the miRNAs that regulate KLF2 and explore its specific mechanism in gastric cancer. Bioinformatics software Targetscan identified that microRNA-32-5p (miRNA-32-5p) may bind to KLF2 mRNA to regulate its expression. In order to verify the regulatory effect of miRNA-32-5p on KLF2, the proliferation and migration assays were performed in both KLF2 overexpression and KLF2 knockdown gastric cancer cells. Dual-Luciferase reporter assay proved that KLF2 could bind to the PTEN promoter to induce its expression. Moreover, research on molecular mechanisms indicated that both miRNA-32-5p and shKLF2 downregulated the expression of PTEN and activated the PI3K/AKT signaling to promote the development of gastric cancer. Targeting miRNA-32-5p and KLF2 is expected to provide new sign and target for gastric cancer treatment.
Krüppel样因子2（KLF2）是锌指家族的成员，由于其在胃癌中表达降低，被认为是一种潜在的肿瘤抑制基因。微小RNA（miRNA）是一类短的非编码单链RNA，与胃癌的发生发展密切相关。本研究旨在探讨调控KLF2的miRNA，并探究其在胃癌中的具体机制。生物信息学软件Targetscan鉴定出微小RNA-32-5p（miRNA-32-5p）可能与KLF2 mRNA结合以调节其表达。为了验证miRNA-32-5p对KLF2的调控作用，在KLF2过表达和KLF2敲低的胃癌细胞中进行了增殖和迁移实验。双荧光素酶报告基因实验证明KLF2可与PTEN启动子结合以诱导其表达。此外，分子机制研究表明，miRNA-32-5p和shKLF2均下调PTEN的表达并激活PI3K/AKT信号通路以促进胃癌的发展。靶向miRNA-32-5p和KLF2有望为胃癌治疗提供新的标志物和靶点。
