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TCF3激活的LINC00152通过调控miR-1182/CDK14轴在骨肉瘤中发挥致癌作用。

TCF3-activated LINC00152 exerts oncogenic role in osteosarcoma through regulating miR-1182/CDK14 axis.

作者信息

Zheng Longlong, Hu Nan, Zhou Xiaozhong

机构信息

Department of Orthopedics, The Second Affiliated Hospital of Suzhou University, Suzhou, Jiangsu, 215008, China; Department of Orthopedics, Chuzhou Medical College of Anhui Medical University, Chuzhou, Anhui, 239000, China.

Department of Intervention and Vascular Surgery, Shanghai Tenth People's Hospital Affiliated to Tongji University, Shanghai, 200000, China.

出版信息

Pathol Res Pract. 2019 Feb;215(2):373-380. doi: 10.1016/j.prp.2018.12.031. Epub 2018 Dec 26.

DOI:10.1016/j.prp.2018.12.031
PMID:30600185
Abstract

Long noncoding RNAs (lncRNAs) have been reported to participate in tumorigenesis and diverse cellular processes in osteosarcoma (OS). However, the role of lncRNA LINC00152 in OS remains elusive. In this study, LINC00152 was highly expressed in osteosarcoma tissues and cell lines. Moreover, MTT and colony formation assays revealed that knockdown of LINC00152 significantly suppressed cell proliferation. The inhibitory effect of LINC00152 knockdown on OS cell migration and invasion was analyzed and demonstrated by transwell assays. Additionally, Chromatin immunoprecipitation (ChIP) and luciferase reporter assays suggested that LINC00152 was transcriptionally activated by the transcription factor TCF3. More importantly, mechanism investigation revealed that LINC00152 was predominantly located in the cytoplasm of OS cells and acted as a competing endogenous RNA (ceRNA) in OS by regulating miR-1182/CDK14 axis. Collectively, LINC00152 was activated by TCF3 and promotes cell proliferation and migration in osteosarcoma via miR-1182-CDK14 axis.

摘要

据报道,长链非编码RNA(lncRNAs)参与骨肉瘤(OS)的肿瘤发生和多种细胞过程。然而,lncRNA LINC00152在骨肉瘤中的作用仍不清楚。在本研究中,LINC00152在骨肉瘤组织和细胞系中高表达。此外,MTT和集落形成试验表明,敲低LINC00152可显著抑制细胞增殖。通过Transwell试验分析并证实了敲低LINC00152对骨肉瘤细胞迁移和侵袭的抑制作用。此外,染色质免疫沉淀(ChIP)和荧光素酶报告试验表明,转录因子TCF3可转录激活LINC00152。更重要的是,机制研究表明,LINC00152主要位于骨肉瘤细胞的细胞质中,并通过调节miR-1182/CDK14轴在骨肉瘤中作为竞争性内源性RNA(ceRNA)发挥作用。总之,LINC00152被TCF3激活,并通过miR-1182-CDK14轴促进骨肉瘤细胞的增殖和迁移。

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