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长链非编码RNA PVT1的上调通过调控MiR-519d-3p和HIF-1A促进胰腺导管腺癌细胞进展和糖酵解。

Upregulation of LncRNA PVT1 Facilitates Pancreatic Ductal Adenocarcinoma Cell Progression and Glycolysis by Regulating MiR-519d-3p and HIF-1A.

作者信息

Sun Junwei, Zhang Pingping, Yin Tao, Zhang Feng, Wang Weixing

机构信息

Department of Hepatobiliary and Laparoscopic Surgery, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, Hubei 430060, China.

Department of Radiation Oncology, Hubei Cancer Hospital, Affiliated Hubei Cancer Hospital of Huazhong University of Science and Technology, 116 Zhuodaoquan South Road, Wuhan, Hubei 430079, China.

出版信息

J Cancer. 2020 Feb 14;11(9):2572-2579. doi: 10.7150/jca.37959. eCollection 2020.

Abstract

The long, noncoding RNA (lncRNA) PVT1, as an important epigenetic regulator, has a critical role in carcinogenesis. However, its role in pancreatic ductal adenocarcinoma (PDAC) has not been fully investigated. Here, the up-regulated expression of lncRNA PVT1 is found in our PDAC tumor samples. Knockdown of it suppressed PDCA cells growth and glycolysis. An inverse association between miR-519d-3p and PVT1 was found. RIP, RNA pulldown and luciferase assay showed that PVT1 directly targets miR-519d-3p by binding with microRNA binding site. Bioinformatics analysis and study indicated that HIF-1A is a target of miR-519d-3p. Collectively, our findings suggested that PVT1 could act as an oncogenic lncRNA, and promote tumor progression by regulating HIF-1A via competing with miR-519d-3p.

摘要

长链非编码RNA(lncRNA)PVT1作为一种重要的表观遗传调节因子,在肿瘤发生过程中起关键作用。然而,其在胰腺导管腺癌(PDAC)中的作用尚未得到充分研究。在此,我们发现lncRNA PVT1在PDAC肿瘤样本中表达上调。敲低该lncRNA可抑制PDCA细胞的生长和糖酵解。研究发现miR-519d-3p与PVT1呈负相关。RNA免疫沉淀(RIP)、RNA下拉实验及荧光素酶实验表明,PVT1通过与微小RNA结合位点结合直接靶向miR-519d-3p。生物信息学分析及研究表明,缺氧诱导因子-1α(HIF-1A)是miR-519d-3p的一个靶标。总的来说,我们的研究结果表明,PVT1可能作为一种致癌lncRNA,通过与miR-519d-3p竞争来调节HIF-1A,从而促进肿瘤进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9199/7066006/28193ef0ced2/jcav11p2572g001.jpg

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