Department of Oncology, The Affiliated Zhongda Hospital of Southeast University, Nanjing, Jiangsu 210029, PR China.
Mol Med Rep. 2012 Sep;6(3):501-6. doi: 10.3892/mmr.2012.946. Epub 2012 Jun 13.
Recent studies have shown that microRNA-146a (miR-146a) is associated with cancer metastasis. However, the mechanisms underlying this process remain poorly understood. In this study, we aimed to investigate the potential role of miR-146a in gastric cancer metastasis. A wound-healing assay and a Transwell assay were used to investigate the impact of miR-146a on the migratory and invasive abilities of MKN-45 cells in vitro. MKN-45 cells stably expressing miR-146a or the negative control were transplanted into nude mice through the lateral tail vein to explore the effect of miR-146a on tumor metastasis in vivo. A luciferase reporter assay and western blot analysis were used to identify the potential target genes. Our results show that the overexpression of miR-146a inhibits the invasion and metastasis of MKN-45 cells in vitro and in vivo. Furthermore, the L1 cell adhesion molecule (L1CAM) was identified as a novel target of miR‑146a in gastric cancer. Taken together, our results provide evidence that miR-146a suppresses gastric cancer cell invasion and metastasis in vitro and in vivo, which may be in part due to the downregulation of L1CAM. miR-146a may have the therapeutic potential to suppress gastric cancer metastasis.
最近的研究表明,微小 RNA-146a(miR-146a)与癌症转移有关。然而,这一过程的机制仍知之甚少。在这项研究中,我们旨在研究 miR-146a 在胃癌转移中的潜在作用。我们使用划痕愈合实验和 Transwell 实验来研究 miR-146a 对 MKN-45 细胞体外迁移和侵袭能力的影响。通过侧尾静脉将稳定表达 miR-146a 或阴性对照的 MKN-45 细胞移植到裸鼠体内,以探讨 miR-146a 对肿瘤转移的影响。荧光素酶报告基因检测和 Western blot 分析用于鉴定潜在的靶基因。我们的结果表明,miR-146a 的过表达抑制了 MKN-45 细胞在体外和体内的侵袭和转移。此外,L1 细胞黏附分子(L1CAM)被鉴定为胃癌中 miR-146a 的一个新的靶基因。综上所述,我们的结果提供了证据表明,miR-146a 抑制了胃癌细胞在体外和体内的侵袭和转移,这可能部分是由于 L1CAM 的下调。miR-146a 可能具有抑制胃癌转移的治疗潜力。