Upregulation of MircoRNA-370 induces proliferation in human prostate cancer cells by downregulating the transcription factor FOXO1.
Upregulation of MircoRNA-370 induces proliferation in human prostate cancer cells by downregulating the transcription factor FOXO1.
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DOI：
10.1371/journal.pone.0045825
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Mao X
中科院分区：
文献类型：
--
作者：
Wu Z;Sun H;Zeng W;He J;Mao X
叉头盒蛋白O 1（FOXO 1）是FOXO家族转录因子的关键成员，作为肿瘤抑制因子，与多种关键细胞功能相关，包括细胞生长、分化、凋亡和血管生成。因此，FOXO蛋白表达在癌细胞中下调的原因令人困惑。MicroRNA是一种非编码的20 ~ 22个核苷酸的单链RNA，可导致靶基因的翻译抑制或降解以及基因沉默，对基因表达的调控起重要作用。在目前的研究中，我们报告说，miR-370的表达显着上调，在5个前列腺癌细胞系相比，正常前列腺上皮细胞（PrEC）。miR-370的异位表达诱导DU 145和LNCaP前列腺癌细胞增殖并增加其非贴壁依赖性生长和集落形成能力，而miR-370的抑制降低增殖、非贴壁依赖性生长和集落形成能力。此外，miR-370的上调促进DU 145和LNCaP前列腺癌细胞进入G1/S细胞周期转换，这与细胞周期蛋白依赖性激酶（CDK）抑制剂p27 Kip 1和p21 Cip 1的下调以及细胞周期调节因子cyclin D1 mRNA的上调有关。此外，我们证明了miR-370可以通过直接靶向FOXO 1的3′-非翻译区来下调FOXO 1的表达。综上所述，我们的研究结果表明，miR-370通过直接抑制肿瘤抑制因子FOXO 1在人前列腺癌细胞的增殖中起着重要作用。
Forkhead box protein O1 (FOXO1), a key member of the FOXO family of transcription factors, acts as a tumor suppressor and has been associated with various key cellular functions, including cell growth, differentiation, apoptosis and angiogenesis. Therefore, it is puzzling why FOXO protein expression is downregulated in cancer cells. MicroRNAs, non-coding 20∼22 nucleotide single-stranded RNAs, result in translational repression or degradation and gene silencing of their target genes, and significantly contribute to the regulation of gene expression. In the current study, we report that miR-370 expression was significantly upregulated in five prostate cancer cell lines, compared to normal prostatic epithelial (PrEC) cells. Ectopic expression of miR-370 induced proliferation and increased the anchorage-independent growth and colony formation ability of DU145 and LNCaP prostate cancer cells, while inhibition of miR-370 reduced proliferation, anchorage-independent growth and colony formation ability. Furthermore, upregulation of miR-370 promoted the entry of DU145 and LNCaP prostate cancer cells into the G1/S cell cycle transition, which was associated with downregulation of the cyclin-dependent kinase (CDK) inhibitors, p27Kip1 and p21Cip1, and upregulation of the cell-cycle regulator cyclin D1 mRNA. Additionally, we demonstrated that miR-370 can downregulate expression of FOXO1 by directly targeting the FOXO1 3′-untranslated region. Taken together, our results suggest that miR-370 plays an important role in the proliferation of human prostate cancer cells, by directly suppressing the tumor suppressor FOXO1.
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影响因子：
5.2
作者：
Kong, Dejuan;Li, Yiwei;Wang, Zhiwei;Banerjee, Sanjeev;Ahmad, Aamir;Kim, Hyeong-Reh Choi;Sarkar, Fazlul H.
通讯作者：
Sarkar, Fazlul H.
影响因子：
3.5
作者：
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影响因子：
254.7
作者：
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通讯作者：
Thun, Michael J.
DOI：
10.1073/pnas.0405454101
发表时间：
2004-09-14
影响因子：
11.1
作者：
Aoki, M;Hao, J;Vogt, PK
通讯作者：
Vogt, PK
DOI：
10.1073/pnas.0406789102
发表时间：
2005-02-01
影响因子：
11.1
作者：
Huang, H;Regan, KM;Tindall, DJ
通讯作者：
Tindall, DJ