Downregulation of S100A4 expression by RNA interference suppresses cell growth and invasion in human colorectal cancer cells.
Downregulation of S100A4 expression by RNA interference suppresses cell growth and invasion in human colorectal cancer cells.
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RNA干扰下调S100A4表达抑制人结直肠癌细胞的生长和侵袭
DOI：
10.3892/or.2011.1598
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发表时间：
2012-04
期刊：
影响因子：
4.2
通讯作者：
Cai S
中科院分区：
文献类型：
--
作者：
Huang L;Xu Y;Cai G;Guan Z;Cai S
S100A4蛋白是钙结合蛋白S100超家族的一员，广泛存在于包括结直肠癌在内的多种人类肿瘤中。我们以往的研究表明，S100A4的过表达与结直肠癌的淋巴转移和预后不良有关，但其在结直肠癌中的生物学作用尚不清楚。在本研究中，我们比较了S100A4在六个大肠癌细胞系中的表达水平，发现其表达水平与其侵袭性大致一致。利用RNA干扰技术，我们抑制了S100A4在具有高侵袭力的SW620结直肠癌细胞和S100A4高表达细胞中的表达。S100A4的特异性敲除可强烈抑制细胞的生长、迁移和侵袭活性。此外，利用转移相关基因mRNA芯片，我们发现S100A4下调后有4个基因表达显著失调(超过2倍)，包括3个下调的基因(MMP9、MMP10和CDH11)和1个上调的基因(TIMP4)。我们目前的研究结果表明，S100A4可能通过多个分子正向调控肿瘤细胞的增殖、侵袭和转移。因此，抑制S100A4可能是一种潜在的治疗结直肠癌的新方法。
S100A4 protein, a member of the S100 superfamily of calcium-binding proteins, is frequently observed in various types of human cancers, including colorectal cancer (CRC). Our previous investigations have demonstrated that the overexpression of S100A4 is associated with lymph node metastasis and poor prognosis in CRC; however, its biological roles in CRC remain unclear. In the present study, we compared the expression of S100A4 at the mRNA and protein levels in six CRC cell lines, and found that the expression levels roughly coincided with their invasiveness. Using RNA interference, we suppressed S100A4 expression in SW620 CRC cells with highly invasive potential and S100A4 high expression. The specific knockdown of S100A4 strongly suppressed cell growth, migration and invasion activities. Furthermore, employing metastasis-related gene mRNA microarrays, we found four genes to be significantly dysregulated (more than 2-fold) after downregulation of S100A4, including three downregulated genes (MMP9, MMP10 and CDH11) and one upregulated gene (TIMP4). Our present results indicate that S100A4 may positively regulate tumor cell proliferation, invasion and metastasis associated with multiple molecules. Thus, the inhibition of S100A4 might be a potentially novel approach to treatment for CRC.
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影响因子：
4
作者：
Mortazavi, Fariborz;Dubinett, Steven;Rettig, Matthew
通讯作者：
Rettig, Matthew
影响因子：
4
作者：
Li, Zhongyong;Zhou, Zhiyi;Donahue, Henry J.
通讯作者：
Donahue, Henry J.
影响因子：
6.5
作者：
Mischke, D;Korge, BP;Ziegler, A
通讯作者：
Ziegler, A
DOI：
10.1016/s0167-4889(98)00143-8
发表时间：
1998-12-10
影响因子：
5.1
作者：
Barraclough, R
通讯作者：
Barraclough, R
影响因子：
254.7
作者：
Parkin, DM;Bray, F;Pisani, P
通讯作者：
Pisani, P