Chen Songda, Wu Huijie, Zhu Lingyu, Jiang Mengjie, Wei Shuli, Luo Jinhua, Liu Aiqun
Department of Endoscopy, Guangxi Medical University Cancer Hospital, Nanning, China.
Department of Gastroenterology, The 10th Affiliated Hospital of Guangxi Medical University, Qinzhou, China.
Front Oncol. 2021 Aug 31;11:728393. doi: 10.3389/fonc.2021.728393. eCollection 2021.
Gastric cancer (GC) is one of the most common malignant tumors. More and more evidences support the role of microRNAs (miRNAs) in tumor progression. However, the role of miRNAs in human GC remains largely unknown.
Based on the published gastric cancer expression profile data, combined with bioinformatics analysis, potential miRNAs in the process of GC were screened. The expression of miR-199b-5p in GC cells and patients' plasma was detected by RT-PCR. The effects of miR-199b-5p on GC were detected by EdU proliferation assay, colony formation assay, Transwell assay and wound healing assay. Western blot was used to detect epithelial-mesenchymal transition (EMT) related proteins. The subcutaneous tumorigenesis model and metastatic tumor model of mice were used to study its effect . Bioinformatics and Dual luciferase reporter assay were used to verify the effect of miR-199b-5p and its target gene.
Through bioinformatics analysis, we screened a novel miRNA miR-199b-5p that was significantly up-regulated in GC tissue and associated with poor prognosis of GC patients. RT-PCR results showed that its expression was also up-regulated in GC cell lines and patients' plasma. MiR-199b-5p can significantly promote GC cell proliferation and migration and . Western blot showed that miR-199b-5p could promote the EMT process of GC. HHIP has been proved to be a target of miR-199b-5p, and the recovery of HHIP can weaken the effect of miR-199b-5p.
MiR-199b-5p may play an oncogene role in GC by targeting , suggesting that miR-199b-5p may be a potential therapeutic target for GC.
胃癌(GC)是最常见的恶性肿瘤之一。越来越多的证据支持微小RNA(miRNA)在肿瘤进展中的作用。然而,miRNA在人类GC中的作用仍 largely未知。
基于已发表的胃癌表达谱数据,结合生物信息学分析,筛选GC过程中的潜在miRNA。通过RT-PCR检测miR-199b-5p在GC细胞和患者血浆中的表达。通过EdU增殖试验、集落形成试验、Transwell试验和伤口愈合试验检测miR-199b-5p对GC的影响。采用蛋白质印迹法检测上皮-间质转化(EMT)相关蛋白。利用小鼠皮下肿瘤发生模型和转移瘤模型研究其作用。采用生物信息学和双荧光素酶报告基因试验验证miR-199b-5p及其靶基因的作用。
通过生物信息学分析,我们筛选出一种新型miRNA miR-199b-5p,其在GC组织中显著上调,并与GC患者的不良预后相关。RT-PCR结果显示,其在GC细胞系和患者血浆中的表达也上调。MiR-199b-5p可显著促进GC细胞增殖和迁移。蛋白质印迹显示,miR-199b-5p可促进GC的EMT过程。HHIP已被证明是miR-199b-5p的靶标,HHIP的恢复可减弱miR-199b-5p的作用。
MiR-199b-5p可能通过靶向 在GC中发挥癌基因作用,提示miR-199b-5p可能是GC的潜在治疗靶点。