The microRNA -23b/-27b cluster suppresses the metastatic phenotype of castration-resistant prostate cancer cells.
The microRNA -23b/-27b cluster suppresses the metastatic phenotype of castration-resistant prostate cancer cells.
复制标题
DOI：
10.1371/journal.pone.0052106
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Burnstein KL
中科院分区：
文献类型：
--
作者：
Ishteiwy RA;Ward TM;Dykxhoorn DM;Burnstein KL
微小RNA（microRNAs，miRs）是一类内源性的非编码小RNA，可调节互补mRNA靶点的稳定性和/或翻译。miR不仅作为正常生理过程的关键调节剂出现，而且它们的失调可能显著影响前列腺癌和其他癌症。与原发性前列腺癌和良性组织相比，由相同的miR簇（miR-23 b/-27 b）编码的miR-23 b和miR-27 b的表达在转移性去势抵抗性肿瘤中下调;然而，它们在前列腺癌进展中的可能作用尚不清楚。我们发现，在两个独立的去势抵抗性前列腺癌细胞系中，miR-23 b/-27 b的异位表达导致侵袭和迁移的抑制，以及在软琼脂中存活率的降低（失巢凋亡的一种测量方法）。然而，miR-23 b/-27 b对细胞增殖没有影响，表明这些miR在前列腺癌中起转移（而不是生长）抑制剂的作用。相反，在侵袭性较低的雄激素依赖性LNCaP前列腺癌细胞系中抑制miR-23 b/-27 b导致增强的侵袭和迁移，也不影响增殖。从机制上讲，我们发现在转移性去势抵抗性前列腺癌细胞系中引入miR-23 b/-27 b导致Rac 1活性显著减弱，而不影响总Rac 1水平，并导致肿瘤抑制因子E-cadherin水平增加。这些miR的抑制在雄激素依赖性LNCaP细胞中具有相反的效果。这些结果表明，miR-23 b/-27 b是转移抑制因子，可能作为新的生物标志物和去势抵抗性疾病的治疗剂。
MicroRNAs (miRs) are small, endogenous, non-coding RNAs that regulate the stability and/or translation of complementary mRNA targets. MiRs have emerged not only as critical modulators of normal physiologic processes, but their deregulation may significantly impact prostate and other cancers. The expression of miR-23b and miR-27b, which are encoded by the same miR cluster (miR-23b/-27b), are downregulated in metastatic, castration-resistant tumors compared to primary prostate cancer and benign tissue; however, their possible role in prostate cancer progression is unknown. We found that ectopic expression of miR-23b/-27b in two independent castration-resistant prostate cancer cell lines resulted in suppression of invasion and migration, as well as reduced survival in soft agar (a measure of anoikis). However, there was no effect of miR-23b/-27b on cell proliferation suggesting that these miRs function as metastasis (but not growth) suppressors in prostate cancer. Conversely, inhibition of miR-23b/-27b in the less aggressive androgen-dependent LNCaP prostate cancer cell line resulted in enhanced invasion and migration also without affecting proliferation. Mechanistically, we found that introduction of miR-23b/-27b in metastatic, castration-resistant prostate cancer cell lines resulted in a significant attenuation of Rac1 activity without affecting total Rac1 levels and caused increased levels of the tumor suppressor E-cadherin. Inhibition of these miRs had the opposite effect in androgen-dependent LNCaP cells. These results suggest that miR-23b/-27b are metastasis suppressors that might serve as novel biomarkers and therapeutic agents for castration-resistant disease.
登录
查看更多内容
影响因子：
11.2
作者：
Bader AG;Brown D;Winkler M
通讯作者：
Winkler M
影响因子：
8.8
作者：
通讯作者：
--
影响因子：
3.9
作者：
Engers, R.;Ziegler, S.;Gabbert, H. E.
通讯作者：
Gabbert, H. E.
影响因子：
2.8
作者：
LOOP, SM;ROZANSKI, TA;OSTENSON, RC
通讯作者：
OSTENSON, RC
影响因子：
4.3
作者：
Ma, Li;Weinberg, Robert A.
通讯作者：
Weinberg, Robert A.