Overexpression of paxillin induced by miR-137 suppression promotes tumor progression and metastasis in colorectal cancer.
Overexpression of paxillin induced by miR-137 suppression promotes tumor progression and metastasis in colorectal cancer.
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DOI：
10.1093/carcin/bgs400
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发表时间：
2013-04
期刊：
影响因子：
4.7
通讯作者：
Xu RH
中科院分区：
文献类型：
--
作者：
Chen DL;Wang DS;Wu WJ;Zeng ZL;Luo HY;Qiu MZ;Ren C;Zhang DS;Wang ZQ;Wang FH;Li YH;Kang TB;Xu RH
桩蛋白（PXN）的失调参与了包括结直肠癌（CRC）在内的多种恶性肿瘤的进展和转移。miR-137在CRC中经常被抑制。PXN被预测为CRC细胞中miR-137的直接靶标。在此基础上，我们假设抑制miR-137诱导的PXN过表达可能促进肿瘤进展和转移，并预测预后不良。采用免疫组化和实时荧光定量PCR方法检测PXN和miR-137在临床肿瘤组织中的表达，247例中PXN阳性198例（80.1%），而癌旁非癌组织中PXN无表达或表达较弱。癌组织中PXN mRNA水平高于癌旁组织，而miR-137水平低于癌旁组织。PXN的高表达和miR-137的低表达与肿瘤的侵袭性表型和不良预后相关。PXN的表达与miR-137的表达呈负相关。双荧光素酶报告基因测定验证了PXN是miR-137的直接靶点。使用miR-137模拟物或抑制剂可以降低或增加CRC细胞系中PXN mRNA和蛋白水平。PXN的敲除或miR-137的异位表达在体外可显著抑制细胞的增殖、迁移和侵袭，在体内可抑制肿瘤的生长和转移。总之，这些结果表明，抑制miR-137诱导的PXN过表达促进肿瘤进展和转移，并可作为CRC患者的独立预后指标。
The deregulation of paxillin (PXN) has been involved in the progression and metastasis of different malignancies including colorectal cancer (CRC). miR-137 is frequently suppressed in CRC. PXN is predicted to be a direct target of miR-137 in CRC cells. On this basis, we hypothesized that overexpression of PXN induced by suppression of miR-137 may promote tumor progression and metastasis and predicts poor prognosis. We detected the expression of PXN and miR-137 in clinical tumor tissues by immunohistochemical analysis and real-time PCR, positive PXN staining was observed in 198 of the 247 (80.1%) cases, whereas no or weak PXN staining was observed in the adjacent non-cancerous area. Higher level of PXN messenger RNA (mRNA) and lower level of miR-137 was observed in cancer tissues than adjacent non-cancerous tissues. High expression of PXN and low expression of miR-137 was associated with aggressive tumor phenotype and adverse prognosis. Moreover, the expression of PXN was negatively correlated with miR-137 expression. A dual-luciferase reporter gene assay validated that PXN was a direct target of miR-137. The use of miR-137 mimics or inhibitor could decrease or increase PXN mRNA and protein levels in CRC cell lines. Knockdown of PXN or ectopic expression of miR-137 could markedly inhibit cell proliferation, migration and invasion in vitro and repress tumor growth and metastasis in vivo. Taken together, these results demonstrated that overexpression of PXN induced by suppression of miR-137 promotes tumor progression and metastasis and could serve as an independent prognostic indicator in CRC patients.
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影响因子：
64.8
作者：
Lu, J;Getz, G;Golub, TR
通讯作者：
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