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本帖最后由 细胞海洋 于 2011-1-19 18:44 编辑
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* [4 b& ?7 c$ N- D2 S题目：miR-34a通过直接抑制CD44来直接抑制前列腺肿瘤干细胞及转移。6 }- u- {( B8 I% }, |: W
说明：原文来源自Nature Medicine由干细胞之家新闻小组成员 tjutiger翻译（转帖请注明）摘要：癌症干细胞（CSCs）,也被称为肿瘤起始细胞，参与了肿瘤的发展与转移过程。MicroRNAs (miRNA)既可以调控正常干细胞也可以调控癌症干细胞，miRNAs的失调被认为与肿瘤发生密切相关。应用细胞黏附分子CD44，或联合应用其他标记物可以鉴定多种肿瘤中的CSCs，如乳腺癌、胰腺癌、头颈部肿瘤、结肠癌、小肠癌、肝癌、胃癌、膀胱癌和卵巢癌。前列腺肿瘤CD44阳性细胞群也富含具有较强体外克隆形成和体内肿瘤形成及转移能力的CSCs，但是，miRNAs是否调控前列腺癌干细胞以及前列腺癌的转移，目前还不清楚。这里我们通过表达水平分析发现，P53的靶标—miR-34a,在CD44阳性的前列腺癌细胞群中表达下调，在同样细胞群中，过表达miR-34a则抑制了细胞的增殖和体内肿瘤形成及转移,相反，在CD44阴性的细胞群导入miR-34a的拮抗物则促进了肿瘤的发展与转移。对前列腺癌的荷瘤小鼠静脉输注miR-34a，抑制了肿瘤的转移同时延长了小鼠的生存时间。我们鉴定并确认了CD44是miR-34a的一个直接的靶标，并发现敲除CD44同时过表达miR-34a能够抑制前列腺癌细胞的肿瘤形成及转移。我们的研究表明：miR-34a是CD44阳性前列腺肿瘤细胞的关键负调控子，为将miR-34a开发为针对前列腺CSCs的治疗药物提供了强大的理论基础。8 ]7 @. H* ^ N: ~+ [/ r
备注：个人翻译，理解不准确的语句还望大家积极指出。
% `4 ?5 v7 A- ~% V+ Z* ^6 o原文链接：http://www.ncbi.nlm.nih.gov/pubmed/21240262; f" q# k, v) v2 ?0 A b6 O
原文abstract:* Z9 v5 q9 m- K- G$ ^1 J6 q* M
Cancer stem cells (CSCs), or tumor-initiating cells, are involved in tumor progression and metastasis. MicroRNAs (miRNAs) regulate both normal stem cells and CSCs, and dysregulation of miRNAs has been implicated in tumorigenesis. CSCs in many tumors-including cancers of the breast, pancreas, head and neck, colon, small intestine, liver, stomach, bladder and ovary-have been identified using the adhesion molecule CD44, either individually or in combination with other marker(s). Prostate CSCs with enhanced clonogenic and tumor-initiating and metastatic capacities are enriched in the CD44(+) cell population, but whether miRNAs regulate CD44(+) prostate cancer cells and prostate cancer metastasis remains unclear. Here we show, through expression analysis, that miR-34a, a p53 target, was underexpressed in CD44(+) prostate cancer cells purified from xenograft and primary tumors. Enforced expression of miR-34a in bulk or purified CD44(+) prostate cancer cells inhibited clonogenic expansion, tumor regeneration, and metastasis. In contrast, expression of miR-34a antagomirs in CD44(-) prostate cancer cells promoted tumor development and metastasis. Systemically delivered miR-34a inhibited prostate cancer metastasis and extended survival of tumor-bearing mice. We identified and validated CD44 as a direct and functional target of miR-34a and found that CD44 knockdown phenocopied miR-34a overexpression in inhibiting prostate cancer regeneration and metastasis. Our study shows that miR-34a is a key negative regulator of CD44(+) prostate cancer cells and establishes a strong rationale for developing miR-34a as a novel therapeutic agent against prostate CSCs.
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- A" d& d+ g: e: ]3 d4 M$ a6楼原文 感谢深海寂寞鱼 提供 |
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发表于 2011-1-18 21:53
发表于 2011-1-18 22:48
