Loss of miR-100 enhances migration, invasion, epithelial-mesenchymal transition and stemness properties in prostate cancer cells through targeting Argonaute 2
Loss of miR-100 enhances migration, invasion, epithelial-mesenchymal transition and stemness properties in prostate cancer cells through targeting Argonaute 2
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miR-100 的缺失通过靶向 Argonaute 2 增强前列腺癌细胞的迁移、侵袭、上皮间质转化和干细胞特性
DOI：
10.3892/ijo.2014.2413
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发表时间：
2014-07-01
影响因子：
5.2
通讯作者：
Peng, Xinsheng
中科院分区：
文献类型：
--
作者：
Wang, Min;Ren, Dong;Peng, Xinsheng
文献证据表明，一些microRNAs （miRNAs）在大多数实体瘤转移中起着关键作用。先前的研究表明，miR-100在人前列腺癌组织中与正常前列腺相比下调，在骨转移性前列腺癌样本中与原发性前列腺癌相比，miR-100也显著降低。Argonaute 2 （AGO2）是mirna诱导沉默复合物的核心效应蛋白，过表达AGO2可能促进肿瘤转移。然而，miR-100和AGO2是否以及如何调控前列腺癌转移尚不清楚。在这里，我们报道miR-100负调控PC-3和DU145细胞的迁移、侵袭、上皮-间质转化（EMT）、集落形成、球状体形成以及严重度因子c-Myc、Oct4和k14f4的表达。此外，miR-100的表达与前列腺癌患者骨转移呈负相关。值得注意的是，荧光素酶检测显示AGO2是miR-100的直接靶点。AGO2下调可抑制前列腺癌细胞的迁移、侵袭、EMT和干性，并逆转miR-100下调的作用。下调AGO2可增强miR-34a和miR-125b的表达，从而抑制癌细胞的迁移、侵袭、EMT和严重度。综上所述，我们的研究结果表明，miR-100的缺失至少部分地通过调节癌细胞的迁移、侵袭、EMT和严重程度，通过上调AGO2的表达来促进前列腺癌细胞的转移能力，并提示miR-100/AGO2可能在调节前列腺癌的转移中发挥重要作用，是预防和治疗的潜在靶点。
Evidence in literature has demonstrated that some microRNAs (miRNAs) play a pivotal role in most solid tumor metastasis. Previous studies have showed that miR-100 is downregulated in human prostate cancer tissue compared to normal prostate and also significantly decreased in bone metastatic prostate cancer samples compared with primary prostate cancer. Argonaute 2 (AGO2) is the core effector protein of the miRNA-induced silencing complex and overexpression of AGO2 might enhance tumor metastasis. However, it is unknown whether and how miR-100 and AGO2 regulates metastasis of prostate cancer. Here, we report that miR-100 negatively regulated migration, invasion, epithelial-mesenchymal transition (EMT), colony formation, spheroid formation and expression of the sternness factors c-Myc, Oct4 and K1f4 in PC-3 and DU145 cells. Furthermore, miR-100 expression was negatively correlated with bone metastasis of prostate cancer patients. Notably, luciferase assay showed that AGO2 was a direct target of miR-100. Downregulation of AGO2 repressed migration, invasion, EMT and stemness of prostate cancer cells, and reversed the effects seen with miR-100 downregulation. Downregulation of AGO2 enhanced expression of miR-34a and miR-125b which can suppress migration, invasion, EMT and sternness of cancer cells. Taken together, our findings indicate that loss of miR-100 promotes the metastatic ability of prostate cancer cells at least partially by upregulating AGO2 expression through modulating migration, invasion, EMT and sternness of cancer cells, and suggest that miR-100/AGO2 may play an important role in regulating the metastasis of prostate cancer and is a potential target of prevention and therapy.