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长链非编码RNA TUG1通过作为骨肉瘤细胞中miR-335-5p的竞争性内源RNA来促进细胞迁移和侵袭。

Long non-coding RNA TUG1 promotes migration and invasion by acting as a ceRNA of miR-335-5p in osteosarcoma cells.

作者信息

Wang Yong, Yang Tao, Zhang Zhen, Lu Ming, Zhao Wei, Zeng Xiandong, Zhang Weiguo

机构信息

The 4th Department of Orthopedic Surgery, Central Hospital Affiliated to Shenyang Medical College, Shenyang, China.

Department of Joint Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China.

出版信息

Cancer Sci. 2017 May;108(5):859-867. doi: 10.1111/cas.13201. Epub 2017 May 19.

Abstract

Long non-coding RNA (lncRNA) have been the focus of increasing attention due to the role they play in many diseases, including osteosarcoma. The function of taurine upregulated gene 1 (TUG1) and its mechanism in osteosarcoma remain unclear. In our research, we found that TUG1 was elevated and correlated with a poor prognosis in osteosarcoma patients. In addition, the following functional experiment showed that decreased TUG1 could remarkably inhibit osteosarcoma cell migration and invasion, indicating that TUG1 functioned as an oncogene in osteosarcoma. Moreover, we revealed that TUG1 and Rho-associated coiled-coil-containing protein kinase 1 (ROCK1), a metastasis-related gene targeted by microRNA-335-5p (miR-335-5p), had the same miR-335-5p combining site. The subsequent luciferase assay verified TUG1 was a target of miR-335-5p. Furthermore, the results of a real-time quantitative PCR showed that TUG1 and miR-335-5p could affect each other's expression. respectively. Finally, we affirmed that TUG1 affected ROCK1 expression and ROCK1-mediated migration/invasion by working as a competitive endogenous RNA (ceRNA) via miR-335-5p. In summary, the findings of this study, based on ceRNA theory, combining the research foundation of miR-335-5p and ROCK1, and taking TUG1 as a new study point, provide new insight into molecular-level reversing migration and invasion of osteosarcoma.

摘要

长链非编码RNA(lncRNA)因其在包括骨肉瘤在内的多种疾病中所起的作用而受到越来越多的关注。牛磺酸上调基因1(TUG1)在骨肉瘤中的功能及其机制仍不清楚。在我们的研究中,我们发现TUG1在骨肉瘤患者中表达升高且与不良预后相关。此外,以下功能实验表明,降低TUG1可显著抑制骨肉瘤细胞的迁移和侵袭,这表明TUG1在骨肉瘤中起癌基因的作用。此外,我们发现TUG1与一种转移相关基因——含Rho相关卷曲螺旋蛋白激酶1(ROCK1),它们具有相同的微小RNA-335-5p(miR-335-5p)结合位点,而miR-335-5p可靶向ROCK1。随后的荧光素酶报告基因检测证实TUG1是miR-335-5p的靶标。此外,实时定量PCR结果表明TUG1和miR-335-5p可相互影响彼此的表达。最后,我们证实TUG1通过作为miR-335-5p的竞争性内源性RNA(ceRNA)来影响ROCK1的表达以及ROCK1介导的迁移/侵袭。总之,本研究基于ceRNA理论,结合miR-335-5p和ROCK1的研究基础,并将TUG1作为新的研究点,为骨肉瘤分子水平上逆转迁移和侵袭提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3017/5448616/4226ea6afb0a/CAS-108-859-g001.jpg

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