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长链非编码 RNA OIP5-AS1 通过靶向 miR-223 加速 CDK14 表达促进骨肉瘤发生。

Long noncoding RNA OIP5-AS1 accelerates CDK14 expression to promote osteosarcoma tumorigenesis via targeting miR-223.

机构信息

Department of Orthopaedics, The Affiliated Huai'an No.1 People's Hospital of Nanjing Medical University, Huaian, Jiangsu, 223300, China.

Department of Oncology, The Affiliated Huai'an No.1 People's Hospital of Nanjing Medical University, Huaian, Jiangsu, 223300, China.

出版信息

Biomed Pharmacother. 2018 Oct;106:1441-1447. doi: 10.1016/j.biopha.2018.07.109. Epub 2018 Jul 24.

DOI:10.1016/j.biopha.2018.07.109
PMID:30119217
Abstract

The critical roles for long non-coding RNAs (lncRNAs) have been demonstrated for series of cancers, including osteosarcoma. Nevertheless, the accurate mechanism of lncRNAs in osteosarcoma is elusive. In this assay, mechanical researches are performed to investigate the effect and mechanism of lncRNA OIP5-AS1 in osteosarcoma tumorigenesis. Results revealed that OIP5-AS1 level was elevated in osteosarcoma tissue and cells. Clinically, OIP5-AS1 high-expression was closely correlated with osteosarcoma patients' poor prognosis. Mechanistically, silenced OIP5-AS1 expression significantly repressed the proliferative ability and accelerated the apoptosis, meanwhile triggered G0/G1 phase cycle arrest in vitro and mice neoplasm growth in vivo. Subsequently, miR-223 was predicted to target the 3'-UTR of OIP5-AS1 and constituted RNA induced silencing complex, which was confirmed by RNA immunoprecipitation and luciferase reporter assay. Besides, miR-223 targeted the CDK14 mRNA 3'-UTR. In conclusion, our study found the critical regulation of OIP5-AS1/miR-223/CDK14 axis on osteosarcoma tumorigenesis, indicating the tumor promoting role of OIP5-AS1 for osteosarcoma.

摘要

长链非编码 RNA(lncRNAs)在多种癌症中发挥着关键作用,包括骨肉瘤。然而,lncRNAs 在骨肉瘤中的准确作用机制仍不清楚。在本研究中,我们进行了力学研究,以探讨 lncRNA OIP5-AS1 在骨肉瘤发生中的作用和机制。结果表明,lncRNA OIP5-AS1 在骨肉瘤组织和细胞中表达上调。临床研究表明,OIP5-AS1 高表达与骨肉瘤患者的不良预后密切相关。机制上,沉默 OIP5-AS1 的表达显著抑制了骨肉瘤细胞的增殖能力,加速了细胞凋亡,并在体外引发 G0/G1 期细胞周期停滞,在体内抑制了小鼠肿瘤的生长。随后,预测 miR-223 可以靶向 OIP5-AS1 的 3'UTR 并形成 RNA 诱导沉默复合物,这一结论通过 RNA 免疫沉淀和荧光素酶报告基因实验得到了验证。此外,miR-223 靶向 CDK14 mRNA 的 3'UTR。综上所述,我们的研究发现 OIP5-AS1/miR-223/CDK14 轴对骨肉瘤的发生具有重要的调控作用,表明 OIP5-AS1 对骨肉瘤具有促进肿瘤的作用。

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