MiRNA-296-3p-ICAM-1 axis promotes metastasis of prostate cancer by possible enhancing survival of natural killer cell-resistant circulating tumour cells.
MiRNA-296-3p-ICAM-1 axis promotes metastasis of prostate cancer by possible enhancing survival of natural killer cell-resistant circulating tumour cells.
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miRNA-296-3p-ICAM-1 轴可能通过增强自然杀伤细胞耐药循环肿瘤细胞的存活来促进前列腺癌的转移
DOI：
10.1038/cddis.2013.458
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发表时间：
2013-11-21
影响因子：
9
通讯作者：
Yu, J.
中科院分区：
文献类型：
--
作者：
Liu, X.;Chen, Q.;Yan, J.;Wang, Y.;Zhu, C.;Chen, C.;Zhao, X.;Xu, M.;Sun, Q.;Deng, R.;Zhang, H.;Qu, Y.;Huang, J.;Jiang, B.;Yu, J.
自然杀伤细胞（NK）在宿主体内清除循环肿瘤细胞（CTCs），进而阻止肿瘤细胞向转移发展，但其机制尚不明确。我们发现miR-296-3p在非转移性人前列腺癌（PCa）细胞系P69中的表达水平远低于源自P69的高转移细胞系M12中的表达水平。我们证明miR-296-3p直接靶向并抑制恶性M12细胞间粘附分子1 （ICAM-1）的表达。来自临床组织微阵列的数据也显示，miR-296-3p在PCa中经常上调，ICAM-1则反向下调。有趣的是，P69中miR-296-3p的异位表达增加了对NK细胞的耐受性，而M12中miR-296-3p的敲低降低了对NK细胞的抗性，这两种表型都可以通过分别在P69和M12中重新表达或沉默ICAM-1来拯救。这些结果在体内也得到了证实，当通过尾静脉注射到胸腺裸鼠体内时，M12中miR-296-3p的下调显示出肺肿瘤转移的发生率降低，而ICAM-1的持续下调则逆转了这一点，增加了ctc向肺的外渗。上述结果表明，新发现的miR-296-3p-ICAM-1轴可能通过提高NK细胞耐药CTC的存活，在介导PCa转移中起关键作用。我们的发现为前列腺癌的治疗和预后提供了新的潜在靶点。
Natural killer (NK) cells are important in host to eliminate circulating tumour cells (CTCs) in turn preventing the development of tumour cells into metastasis but the mechanisms are very poorly defined. Here we find that the expression level of miR-296-3p is much lower in the non-metastatic human prostate cancer (PCa) cell line P69 than that in the highly metastatic cell line M12, which is derived from P69. We demonstrate that miR-296-3p directly targets and inhibits the expression of intercellular adhesion molecule 1 (ICAM-1) in the malignant M12. The data from clinical tissue microarrays also show that miR-296-3p is frequently upregulated and ICAM-1 is reversely downregulated in PCa. Interestingly, ectopic expression of miR-296-3p in P69 increases the tolerance to NK cells whereas knockdown of miR-296-3p in M12 reduces the resistance to NK cells, which both phenotypes can be rescued by re-expression or silencing of ICAM-1 in P69 and M12, respectively. These results are also manifested in vivo by the decrease in the incidence of pulmonary tumour metastasis exhibited by knockdown of miR-296-3p in M12 when injected into athymic nude mice via tail vein, and consistently down-expression of ICAM-1 reverses this to increase extravasation of CTCs into lungs. Above results suggest that this newly identified miR-296-3p-ICAM-1 axis has a pivotal role in mediating PCa metastasis by possible enhancing survival of NK cell-resistant CTC. Our findings provide novel potential targets for PCa therapy and prognosis.
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影响因子：
14.9
作者：
Chen C;Ridzon DA;Broomer AJ;Zhou Z;Lee DH;Nguyen JT;Barbisin M;Xu NL;Mahuvakar VR;Andersen MR;Lao KQ;Livak KJ;Guegler KJ
通讯作者：
Guegler KJ
影响因子：
4.5
作者：
Klingemann, HG;Martinson, J
通讯作者：
Martinson, J
影响因子：
6.4
作者：
BAE, VL;JACKSONCOOK, CK;WARE, JL
通讯作者：
WARE, JL
影响因子：
2.7
作者：
Himmelreich, Heike;Mathys, Arina;Kalberer, Christian P.
通讯作者：
Kalberer, Christian P.
DOI：
10.1007/978-1-61779-108-6_6
发表时间：
2011-01-01
期刊：
MAMMALIAN CELL VIABILITY: METHODS AND PROTOCOLS
影响因子：
--
作者：
Ke, Ning;Wang, Xiaobo;Abassi, Yama A.
通讯作者：
Abassi, Yama A.