The microRNA-23b/-27b cluster suppresses prostate cancer metastasis via Huntingtin-interacting protein 1-related.
The microRNA-23b/-27b cluster suppresses prostate cancer metastasis via Huntingtin-interacting protein 1-related.
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DOI：
10.1038/onc.2016.6
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发表时间：
2016-09-08
期刊：
影响因子：
8
通讯作者：
Burnstein KL
中科院分区：
文献类型：
--
作者：
Rice MA;Ishteiwy RA;Magani F;Udayakumar T;Reiner T;Yates TJ;Miller P;Perez-Stable C;Rai P;Verdun R;Dykxhoorn DM;Burnstein KL
microRNAs （miRs）的失调有助于前列腺和其他癌症的进展和转移。miR-23b和-27b编码在同一个miR簇（miR-23b/-27b）中，与原发肿瘤和良性组织相比，在人类转移性前列腺癌中miR-23b和-27b被下调。miR-23b/-27b的表达可减少前列腺癌细胞的迁移、侵袭，导致前列腺癌耐药。相反，拮抗剂介导的miR-23b和-27b沉默在更惰性的前列腺癌细胞系中产生相反的结果。然而，miR-23b/-27b的表达和抑制都不影响前列腺癌细胞的增殖，这表明miR-23b/-27b选择性地抑制转移。为了研究miR-23b/-27b对体内前列腺癌转移的影响，我们使用miR-23b/-27b或非靶向对照miRNA转导的侵袭性前列腺癌细胞建立原位前列腺异种移植物。虽然miR-23b/-27b转导的细胞和对照组之间的原发性肿瘤形成相似，但前列腺癌细胞中miR-23b/-27b的表达减少了精囊浸润和远处转移。基因表达谱鉴定了内吞接头，亨廷顿蛋白相互作用蛋白1相关（HIP1R）被miR-23b/-27b下调。前列腺癌细胞中HIP1R表达的增加与miR-23b/-27b过表达对迁移、侵袭和非锚定生长的影响呈负相关。HIP1R挽救了miR-23b/-27b介导的前列腺癌细胞迁移抑制。与混杂的对照组相比，携带miR-23b/-27b转导的前列腺癌细胞异种移植小鼠的精囊组织中HIP1R mRNA水平降低，这表明HIP1R是miR-23b/-27b的关键功能靶点。此外，HIP1R的缺失导致更圆润，更少间充质样细胞形态，与转移性降低一致。总之，这些数据表明miR-23b/-27b簇通过降低前列腺癌临床前模型中的HIP1R水平而发挥转移抑制作用。
Deregulation of microRNAs (miRs) contributes to progression and metastasis of prostate and other cancers. miR-23b and -27b, encoded in the same miR cluster (miR-23b/-27b), are downregulated in human metastatic prostate cancer compared with primary tumors and benign tissue. Expression of miR-23b/-27b decreases prostate cancer cell migration, invasion and results in anoikis resistance. Conversely, antagomiR-mediated miR-23b and -27b silencing produces the opposite result in a more indolent prostate cancer cell line. However, neither miR-23b/-27b expression or inhibition impacts prostate cancer cell proliferation suggesting that miR-23b/-27b selectively suppresses metastasis. To examine the effects of miR-23b/-27b on prostate cancer metastasis in vivo, orthotopic prostate xenografts were established using aggressive prostate cancer cells transduced with miR-23b/-27b or non-targeting control miRNA. Although primary tumor formation was similar between miR-23b/-27b-transduced cells and controls, miR-23b/-27b expression in prostate cancer cells decreased seminal vesicle invasion and distant metastases. Gene-expression profiling identified the endocytic adaptor, Huntingtin-interacting protein 1-related (HIP1R) as being downregulated by miR-23b/-27b. Increased HIP1R expression in prostate cancer cells inversely phenocopied the effects of miR-23b/-27b overexpression on migration, invasion and anchorage-independent growth. HIP1R rescued miR-23b/-27b-mediated repression of migration in prostate cancer cells. HIP1R mRNA levels were decreased in seminal vesicle tissue from mice bearing miR-23b/-27b-transduced prostate cancer cell xenografts compared with scrambled controls, suggesting HIP1R is a key functional target of miR-23b/-27b. In addition, depletion of HIP1R led to a more rounded, less mesenchymal-like cell morphology, consistent with decreased metastatic properties. Together, these data demonstrate that the miR-23b/-27b cluster functions as a metastasis-suppressor by decreasing HIP1R levels in pre-clinical models of prostate cancer.
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影响因子：
56.9
作者：
Lagos-Quintana, M;Rauhut, R;Tuschl, T
通讯作者：
Tuschl, T
前列腺癌的基因表达谱揭示了多个分子途径在转移过程中的参与。
影响因子：
3.8
作者：
Chandran, Uma R.;Ma, Changqing;Dhir, Rajiv;Bisceglia, Michelle;Lyons-Weiler, Maureen;Liang, Wenjing;Michalopoulos, George;Becich, Michael;Monzon, Federico A.
通讯作者：
Monzon, Federico A.
影响因子：
4.2
作者：
Baines AT;Xu D;Der CJ
通讯作者：
Der CJ
影响因子：
3.9
作者：
Gottfried, Irit;Ehrlich, Marcelo;Ashery, Uri
通讯作者：
Ashery, Uri
影响因子：
2.8
作者：
LOOP, SM;ROZANSKI, TA;OSTENSON, RC
通讯作者：
OSTENSON, RC