Knockdown of hMex-3A by small RNA interference suppresses cell proliferation and migration in human gastric cancer cells
Knockdown of hMex-3A by small RNA interference suppresses cell proliferation and migration in human gastric cancer cells
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通过小 RNA 干扰敲低 hMex-3A 可抑制人胃癌细胞的细胞增殖和迁移。
DOI：
10.3892/mmr.2012.943
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发表时间：
2012-09-01
影响因子：
3.4
通讯作者：
Yang, Changqing
中科院分区：
文献类型：
--
作者：
Jiang, Hong;Zhang, Xuemei;Yang, Changqing
RNA结合蛋白（RBP）在RNA代谢中起重要作用，调节RNA的剪接、转运、监视、降解和翻译。RBP的异常表达导致基因表达改变，并经常导致各种疾病，如癌症。在这项研究中，我们首次提供证据表明hMex-3A（一种属于人Mex-3家族的RBP，具有两个K-同源RNA结合结构域）参与肿瘤发生的调节。我们表明，沉默hMex-3A的小干扰RNA有效地抑制细胞增殖SNU-16和AGS胃癌细胞。流式细胞术分析证实了这种对SNU-16细胞生长的影响，并表明hMex-3A可能在G1/M期发挥作用。值得注意的是，hMex-3A敲低也降低了SNU-16和AGS细胞在软琼脂中殖民地形成能力，这意味着hMex-3A是细胞转化所必需的。此外，通过Transwell小室和伤口愈合实验，hMex-3A敲低显著影响BCG-823细胞的迁移能力。通过实时定量PCR使用22对胃癌标本进行的临床相关性分析显示，与匹配的相邻非癌组织相比，hMex-3A在癌组织中显著上调（63.6%）。综上所述，这些结果表明，hMex-3A作为一个癌基因候选人在胃癌的发展和转移的功能，因此它可能作为一个潜在的目标，为肿瘤的治疗。
RNA-binding proteins (RBPs) play essential roles in RNA metabolism, regulating RNA splicing, transport, surveillance, decay and translation. The aberrant expression of RBPs leads to gene expression alteration and frequently causes various diseases, such as cancer. In this study, we are the first to provide evidence that hMex-3A, a RBP that belongs to the human Mex-3 family with two K-homology RNA-binding domains, is involved in the regulation of tumorigenesis. We show that the silencing of hMex-3A by small interference RNA effectively inhibits cell proliferation in SNU-16 and AGS gastric cancer cells. Flow cytometry analysis confirmed this effect on SNU-16 cell growth and indicated that hMex-3A may function in the G1/M phase. Notably, hMex-3A knockdown also reduced the colony formation ability of SNU-16 and AGS cells in soft agar, implying that hMex-3A is required for cell transformation. Furthermore, the hMex-3A knockdown markedly affected the migratory ability of BCG-823 cells by Transwell chamber and wound healing assays. Clinical relevance analysis using 22 paired gastric cancer specimens by quantitative real-time PCR showed that hMex-3A was significantly upregulated (63.6%) in cancer tissues compared with matched adjacent non-cancerous tissues. Taken together, these results suggest that hMex-3A functions as an oncogene candidate in the development and metastasis of gastric cancer; thus it may serve as a potential target for the therapy of tumors.