Zhang P, Tang W M, Zhang H, Li Y Q, Peng Y, Wang J, Liu G N, Huang X T, Zhao J J, Li G, Li A M, Bai Y, Chen Y, Ren Y X, Li G X, Wang Y D, Liu S D, Wang J D
Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Department of Gastroenterology, Hexian Memorial Affiliated Hospital of Southern Medical University, Guangzhou 511400, China.
Br J Cancer. 2017 Aug 8;117(4):525-534. doi: 10.1038/bjc.2017.181. Epub 2017 Jun 20.
MiR-646 has been reported to be aberrantly expressed in human cancers. However, the underlying molecular mechanisms of action of miR-646 in gastric cancer (GC) have not yet been investigated.
In vitro function of miR-646 in GC was evaluated using EdU assay, plate colony formation assay, and matrigel invasion assay. Real-time PCR or western blotting was performed to detect miR-646 and FOXK1 expressions. In vivo tumour growth and metastasis were conducted in nude mice.
MiR-646 expression was downregulated in GC tissues compared with adjacent normal tissues. Low miR-646 expression is associated with malignant progression. Transient transfection of GC cells with miR-646 inhibited their growth and migration. Moreover, miR-646 influenced the expression of epithelial-mesenchymal transition (EMT)-associated proteins. TGF-β1 treatment significantly suppressed the expression of miR-646 and overexpression of this microRNA counteracted the influence of the TGF-β1-induced EMT phenotype. In terms of the underlying mechanism, miR-646 directly targeted FOXK1. In vivo, it inhibited the FOXK1-mediated proliferation and EMT-induced metastasis. Consistently, inverse correlations were also observed between the expression of miR-646 and FOXK1 in human GC tissue samples. Furthermore, miR-646 regulated Akt/mTOR signalling after FOXK1.
miR-646 inhibited GC cell proliferation and the EMT progression in GC cells by targeting FOXK1.
据报道，miR-646在人类癌症中表达异常。然而，miR-646在胃癌（GC）中的潜在分子作用机制尚未得到研究。
使用EdU检测、平板克隆形成检测和基质胶侵袭检测评估miR-646在GC中的体外功能。进行实时PCR或蛋白质印迹以检测miR-646和FOXK1的表达。在裸鼠中进行体内肿瘤生长和转移实验。
与相邻正常组织相比，GC组织中miR-646的表达下调。低miR-646表达与恶性进展相关。用miR-646瞬时转染GC细胞可抑制其生长和迁移。此外，miR-646影响上皮-间质转化（EMT）相关蛋白的表达。TGF-β1处理显著抑制miR-646的表达，而这种 microRNA 的过表达抵消了TGF-β1诱导的EMT表型的影响。就潜在机制而言，miR-646直接靶向FOXK1。在体内，它抑制FOXK1介导的增殖和EMT诱导的转移。同样，在人类GC组织样本中也观察到miR-646和FOXK1表达之间呈负相关。此外，miR-646在FOXK1之后调节Akt/mTOR信号通路。
miR-646通过靶向FOXK1抑制GC细胞增殖和GC细胞中的EMT进展。
