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miRNA-146a 靶向 L1 细胞黏附分子并抑制胃癌的转移潜能。

microRNA-146a targets the L1 cell adhesion molecule and suppresses the metastatic potential of gastric cancer.

机构信息

Department of Oncology, The Affiliated Zhongda Hospital of Southeast University, Nanjing, Jiangsu 210029, PR China.

出版信息

Mol Med Rep. 2012 Sep;6(3):501-6. doi: 10.3892/mmr.2012.946. Epub 2012 Jun 13.

Abstract

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.

摘要

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。

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