The putative tumour suppressor miR-1-3p modulates prostate cancer cell aggressiveness by repressing E2F5 and PFTK1.
The putative tumour suppressor miR-1-3p modulates prostate cancer cell aggressiveness by repressing E2F5 and PFTK1.
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假定的肿瘤抑制因子 miR-1-3p 通过抑制 E2F5 和 PFTK1 来调节前列腺癌细胞的侵袭性
DOI：
10.1186/s13046-018-0895-z
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发表时间：
2018-09-05
期刊：
影响因子：
--
通讯作者：
Hu J
中科院分区：
文献类型：
--
作者：
Li SM;Wu HL;Yu X;Tang K;Wang SG;Ye ZQ;Hu J
研究背景miR-1- 3 p是microRNA-1家族（miR-1）的成员，在多种肿瘤中具有抑癌作用。然而，miR-1 - 3 p在前列腺癌（PCa）中的生物学作用及其内在调控机制尚不清楚。进一步检测miR-1- 3 p的体外和体内功能效应。A luciferase reporter assay was conducted to confirm target associations.ResultsWe found that miR-1-3p was significantly downregulated in advanced PCa tissues and cell lines.低miR-1- 3 p水平与PCa患者的侵袭性临床病理特征和不良预后密切相关。miR-1- 3 p在22 RV 1和LncaP细胞中的异位表达足以在体外和体内阻止肿瘤细胞生长和细胞周期进展。进一步的机制研究表明，miR-1- 3 p可直接靶向E2 F5和PFTK 1两个细胞周期调控基因的mRNA 3′-非翻译区（3′- UTR），抑制其mRNA和蛋白的表达。此外，E2 F5和PFTK 1的敲低模拟了miR-1- 3 p过表达对PCa进展的肿瘤抑制作用。相反，伴随敲低的miR-1- 3 p和E2 F5和PFTK 1实质上逆转了E2 F5或PFTK 1沉默单独的抑制作用。ConclusionThese data highlight a important role for miR-1- 3 p in the regulation of proliferation and cell cycle in the molecular toxicity of PCa and indicate the potential for miR-1- 3 p in applications following PCa acidistics and therapeutics.
BackgroundPrevious studies report that miR-1-3p, a member of the microRNA-1 family (miR-1), and functions as a tumor suppressor in several different cancers. However, little is known regarding the biological role and intrinsic regulatory mechanisms of miR-1-3p in prostate cancer (PCa).MethodsIn this study, the expression levels of miR-1-3p were first examined in PCa cell lines and tumor tissues by RT-qPCR and bioinformatics. The in vitro and in vivo functional effect of miR-1-3p was examined further. A luciferase reporter assay was conducted to confirm target associations.ResultsWe found that miR-1-3p was significantly downregulated in advanced PCa tissues and cell lines. Low miR-1-3p levels were strongly associated with aggressive clinicopathological features and poor prognosis in PCa patients. Ectopic expression of miR-1-3p in 22RV1 and LncaP cells was sufficient to prevent tumor cell growth and cell cycle progression in vitro and in vivo. Further mechanistic studies revealed that miR-1-3p could directly target the mRNA 3′- untranslated region (3′- UTR) of two central cell cycle genes, E2F5 and PFTK1, and could suppress their mRNA and protein expression. In addition, knockdown of E2F5 and PFTK1 mimicked the tumor-suppressive effects of miR-1-3p overexpression on PCa progression. Conversely, concomitant knockdown of miR-1-3p and E2F5 and PFTK1 substantially reversed the inhibitory effects of either E2F5 or PFTK1 silencing alone.ConclusionThese data highlight an important role for miR-1-3p in the regulation of proliferation and cell cycle in the molecular etiology of PCa and indicate the potential for miR-1-3p in applications furthering PCa prognostics and therapeutics.
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影响因子：
254.7
作者：
Siegel, Rebecca;Ma, Jiemin;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin
影响因子：
2
作者：
Luu HN;Lin HY;Sørensen KD;Ogunwobi OO;Kumar N;Chornokur G;Phelan C;Jones D;Kidd L;Batra J;Yamoah K;Berglund A;Rounbehler RJ;Yang M;Lee SH;Kang N;Kim SJ;Park JY;Di Pietro G
通讯作者：
Di Pietro G
影响因子：
64.8
作者：
Denli, AM;Tops, BBJ;Hannon, GJ
通讯作者：
Hannon, GJ
影响因子：
12.4
作者：
Donzelli, S.;Fontemaggi, G.;Blandino, G.
通讯作者：
Blandino, G.
影响因子：
3.4
作者：
Mao, Youjun;Jia, Yuqing;Li, Xiaoqiang
通讯作者：
Li, Xiaoqiang