An Jia-Xiang, Ma Ming-Hui, Zhang Chun-Dong, Shao Shuai, Zhou Nuo-Ming, Dai Dong-Qiu
Department of Gastroenterological Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang, 110032 China.
Cancer Cell Int. 2018 May 1;18:66. doi: 10.1186/s12935-018-0560-9. eCollection 2018.
MicroRNAs deregulation are common in human tumor progression. miR-1236-3p has been reported to function as tumor suppressor microRNA in various malignancies. The aim of this study was to demonstrate the downregulated expression of miR-1236-3p in gastric cancer (GC) tissues and cell lines, and clarify its biological function in GC.
Real-time polymerase chain reaction was used to measure the mRNA level of miR-1236-3p in GC. Dual luciferase assay was used to demonstrate that MTA2 was one of the candidate target genes of miR-1236-3p. Western blots were utilized to detect the protein levels. Cell function assays were also performed to determine the function of miR-1236-3p in GC.
miR-1236-3p expression, which was associated with lymph node metastasis, differentiation and clinical stage, was significantly reduced in GC tissues and cell lines. miR-1236-3p over-expression could inhibit GC cell proliferation, migration and invasion, and inhibition of miR-1236-3p expression had opposite effects. Furthermore, we demonstrated that MTA2 was a candidate target of miR-1236-3p, and miR-1236-3p over-expression significantly inhibited the process of epithelial-mesenchymal transition. We also found that miR-1236-3p could suppress the PI3K/Akt signaling pathway in GC cells.
Our results suggest that miR-1236-3p functions as a tumor suppressor in GC and could be a promising therapeutic target for GC.
微小RNA失调在人类肿瘤进展中很常见。据报道,miR-1236-3p在多种恶性肿瘤中发挥肿瘤抑制微小RNA的作用。本研究的目的是证明miR-1236-3p在胃癌(GC)组织和细胞系中的表达下调,并阐明其在GC中的生物学功能。
采用实时聚合酶链反应检测GC中miR-1236-3p的mRNA水平。采用双荧光素酶报告基因检测法证明MTA2是miR-1236-3p的候选靶基因之一。利用蛋白质免疫印迹法检测蛋白质水平。还进行了细胞功能试验以确定miR-1236-3p在GC中的功能。
miR-1236-3p的表达与淋巴结转移、分化及临床分期相关,在GC组织和细胞系中显著降低。miR-1236-3p过表达可抑制GC细胞的增殖、迁移和侵袭,而抑制miR-1236-3p表达则产生相反的效果。此外,我们证明MTA2是miR-1236-3p的候选靶点,miR-1236-3p过表达显著抑制上皮-间质转化过程。我们还发现miR-1236-3p可抑制GC细胞中的PI3K/Akt信号通路。
我们的结果表明,miR-1236-3p在GC中发挥肿瘤抑制作用,可能是GC有前景的治疗靶点。