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长链非编码 RNA SET 结合因子 2-反义 RNA1 通过靶向 miR-431-5p/CDK14 轴促进人甲状腺乳头状癌细胞生长。

Long noncoding RNAs SET-binding factor 2-antisense RNA1 promotes cell growth through targeting miR-431-5p/CDK14 axis in human papillary thyroid cancer.

机构信息

Department of Nuclear Medicine, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China.

Institute of Pharmacy, North Sichuan Medical College, Nanchong, Sichuan, China.

出版信息

Kaohsiung J Med Sci. 2020 Oct;36(10):808-816. doi: 10.1002/kjm2.12259. Epub 2020 Jun 30.

Abstract

Papillary thyroid cancer (PTC) is a frequent thyroid malignancy. With the significant regulatory role in tumor progression, more attention has been employed to investigate mechanism of long noncoding RNAs (lncRNAs) in progression of PTC. We prospectively explored the mechanism whereby lncRNA SET-binding factor 2-antisense RNA1 (SBF2-AS1) is implicated in pathogenesis of PTC. First, differentially expressed SBF2-AS1 between PTC and normal adjacent thyroid tissues was determined, and result indicated a higher SBF2-AS1 expression in PTC tissues than adjacent normal tissues. Moreover, highly SBF2-AS1 expression predicted a poor prognosis in PTC patients. Second, SBF2-AS1 overexpression promoted cell viability and cycle of PTC, while inhibited cell apoptosis. However, SBF2-AS1 downregulation reduced viability and cycle, while promoted cell apoptosis. Moreover, SBF2-AS1 could bind with miR-431-5p and showed negative correlation with miR-431-5p in PTC patients. Furthermore, miR-431-5p bind with cyclin-dependent kinase (CDK) 14 and showed negative correlation with CDK14 in PTC patients. Finally, overexpression of CDK14 counteracted with the inhibitory role of SBF2-AS1 downregulation on cell viability, cycle, and apoptosis of PTC. In conclusion, SBF2-AS1 exhibited oncogenic property in PTC, and knockdown of SBF2-AS1 could be a therapeutic strategy for PTC.

摘要

甲状腺乳头状癌(PTC)是一种常见的甲状腺恶性肿瘤。由于长链非编码 RNA(lncRNA)在肿瘤进展中的重要调控作用,人们越来越关注其在 PTC 进展中的作用机制。我们前瞻性地探讨了 lncRNA SET 结合因子 2 反义 RNA1(SBF2-AS1)在 PTC 发病机制中的作用机制。首先,我们确定了 PTC 和正常甲状腺组织之间 SBF2-AS1 的差异表达,结果表明 PTC 组织中 SBF2-AS1 的表达高于相邻正常组织。此外,高 SBF2-AS1 表达预示着 PTC 患者预后不良。其次,SBF2-AS1 过表达促进 PTC 细胞的活力和周期,而抑制细胞凋亡。然而,SBF2-AS1 的下调降低了细胞活力和周期,而促进了细胞凋亡。此外,SBF2-AS1 可以与 miR-431-5p 结合,并且与 PTC 患者的 miR-431-5p 呈负相关。此外,miR-431-5p 与细胞周期蛋白依赖性激酶(CDK)14 结合,并且与 PTC 患者的 CDK14 呈负相关。最后,CDK14 的过表达抵消了 SBF2-AS1 下调对 PTC 细胞活力、周期和凋亡的抑制作用。总之,SBF2-AS1 在 PTC 中表现出致癌作用,下调 SBF2-AS1 可能是 PTC 的一种治疗策略。

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