miR-216a inhibits osteosarcoma cell proliferation, invasion and metastasis by targeting CDK14.
miR-216a inhibits osteosarcoma cell proliferation, invasion and metastasis by targeting CDK14.
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miR-216a通过靶向CDK14抑制骨肉瘤细胞增殖、侵袭和转移。
DOI：
10.1038/cddis.2017.499
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发表时间：
2017-10-12
影响因子：
9
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Ji Q;Xu X;Li L;Goodman SB;Bi W;Xu M;Xu Y;Fan Z;Maloney WJ;Ye Q;Wang Y
骨肉瘤（OS）已成为影响儿童和年轻人的最常见的原发性肌肉骨骼恶性肿瘤。细胞周期蛋白依赖性激酶（CDK）与肿瘤生物学中的基因调控密切相关。越来越多的证据表明，CDK14 的异常功能与多种疾病有关，并与临床结果相关。 MicroRNA (miRNA) 是 OS 发展中至关重要的表观遗传调节因子。然而，CDK14的重要作用以及miRNA在OS的肿瘤发生和进展中调节CDK14的分子机制尚未完全阐明。在这里我们发现CDK14表达与OS患者的不良预后和总生存期密切相关。使用双荧光素酶报告基因检测，我们还发现 miR-216a 通过与 CDK14 的 3'非翻译区结合来抑制 CDK14 的表达。 miR-216a 的过表达通过抑制 CDK14 的产生，显着抑制体内和体外的细胞增殖、迁移和侵袭。在转染miR-216a的OS细胞中CDK14的过表达有效地挽救了miR-216a引起的细胞增殖、迁移和侵袭的抑制。此外，Kaplan-Meier 分析表明 miR-216a 表达预示着 OS 患者良好的临床结果。此外，miR-216a 表达在 OS 患者中下调，并且与 CDK14 表达呈负相关。总体而言，这些数据强调了 miR-216a/CDK14 轴作为新型多效性调节剂的作用，并证明了相关的分子机制，从而表明 miR-216a 激活和 CDK14 抑制可能是治疗 OS 患者的新颖且有吸引力的治疗策略。
Osteosarcoma (OS) has emerged as the most common primary musculoskeletal malignant tumour affecting children and young adults. Cyclin-dependent kinases (CDKs) are closely associated with gene regulation in tumour biology. Accumulating evidence indicates that the aberrant function of CDK14 is involved in a broad spectrum of diseases and is associated with clinical outcomes. MicroRNAs (miRNAs) are crucial epigenetic regulators in the development of OS. However, the essential role of CDK14 and the molecular mechanisms by which miRNAs regulate CDK14 in the oncogenesis and progression of OS have not been fully elucidated. Here we found that CDK14 expression was closely associated with poor prognosis and overall survival of OS patients. Using dual-luciferase reporter assays, we also found that miR-216a inhibits CDK14 expression by binding to the 3′-untranslated region of CDK14. Overexpression of miR-216a significantly suppressed cell proliferation, migration and invasion in vivo and in vitro by inhibiting CDK14 production. Overexpression of CDK14 in the miR-216a-transfected OS cells effectively rescued the suppression of cell proliferation, migration and invasion caused by miR-216a. In addition, Kaplan–Meier analysis indicated that miR-216a expression predicted favourable clinical outcomes for OS patients. Moreover, miR-216a expression was downregulated in OS patients and was negatively associated with CDK14 expression. Overall, these data highlight the role of the miR-216a/CDK14 axis as a novel pleiotropic modulator and demonstrate the associated molecular mechanisms, thus suggesting the intriguing possibility that miR-216a activation and CDK14 inhibition may be novel and attractive therapeutic strategies for treating OS patients.
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影响因子：
2.6
作者：
He X;Gao Z;Xu H;Zhang Z;Fu P
通讯作者：
Fu P
DOI：
10.3322/caac.21244
发表时间：
2014-09
期刊：
CA: a cancer journal for clinicians
影响因子：
--
作者：
Berindan-Neagoe I;Monroig Pdel C;Pasculli B;Calin GA
通讯作者：
Calin GA
癌症中的microRNA生物发生途径。
DOI：
10.1038/nrc3932
发表时间：
2015-06
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Lin S;Gregory RI
通讯作者：
Gregory RI
影响因子：
13.5
作者：
Chen, Po-Jen;Yeh, Shiou-Hwei;Chen, Pei-Jer
通讯作者：
Chen, Pei-Jer
影响因子：
16.1
作者：
Caputo M;Saif J;Rajakaruna C;Brooks M;Angelini GD;Emanueli C
通讯作者：
Emanueli C