Ding Dayong, Hou Ruizhi, Gao Yongjian, Feng Ye
Department of Gastrointestinal Surgery, China-Japan Union Hospital, Jilin University, Changchun, Jilin 130000, P.R. China.
Exp Ther Med. 2018 Feb;15(2):1735-1741. doi: 10.3892/etm.2017.5546. Epub 2017 Nov 23.
MicroRNA (miR)-613 has been reported to function as a tumor suppressor in several types of cancer. However, the biological function and underlying mechanism in gastric cancer (GC) has remained elusive. Therefore, the aim of the present study was to assess the expression and biological role of miR-613 in GC tissues and cell lines. miR-613 expression was found to be downregulated in 38 GC tissue samples compared to that in their adjacent non-cancerous tissues, and low expression of miR-613 was associated with lymph node metastasis and advanced tumor-nodes-metastasis stage. A gain-of-function assay demonstrated that miR-613 overexpression reduced tumor cell proliferation, migration and invasion of SGC-7901 cells, as determined by MTT and Transwell assays. Furthermore, brain-derived neutrophic factor (BDNF) was identified as a direct target of miR-613 in GC cells by a luciferase reporter assay. BDNF expression was upregulated and inversely correlated with miR-613 levels in GC tissues. In addition, knockdown of BDNF expression mimicked the tumor suppressive effect of miR-613 in GC cells. In conclusion, these findings demonstrated that miR-613 functions as a tumor suppressor in GC by targeting BDNF. Thus, miR-613 is a potential therapeutic target for GC.
据报道，微小RNA（miR）-613在多种癌症中发挥肿瘤抑制作用。然而，其在胃癌（GC）中的生物学功能及潜在机制仍不清楚。因此，本研究旨在评估miR-613在GC组织和细胞系中的表达及生物学作用。研究发现，与癌旁组织相比，38例GC组织样本中miR-613表达下调，且miR-613低表达与淋巴结转移及肿瘤-淋巴结-转移（TNM）晚期相关。功能获得实验表明，通过MTT和Transwell实验测定，miR-613过表达可降低SGC-7901细胞的肿瘤细胞增殖、迁移和侵袭能力。此外，通过荧光素酶报告基因实验确定脑源性神经营养因子（BDNF）是GC细胞中miR-613的直接靶点。在GC组织中，BDNF表达上调且与miR-613水平呈负相关。此外，敲低BDNF表达可模拟miR-613在GC细胞中的肿瘤抑制作用。总之，这些发现表明miR-613通过靶向BDNF在GC中发挥肿瘤抑制作用。因此，miR-613是GC的一个潜在治疗靶点。
