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长链非编码RNA MIR31HG在胰腺导管腺癌中具有致癌特性，并受miR-193b负调控。

Long noncoding RNA MIR31HG exhibits oncogenic property in pancreatic ductal adenocarcinoma and is negatively regulated by miR-193b.

作者信息

Yang H, Liu P, Zhang J, Peng X, Lu Z, Yu S, Meng Y, Tong W-M, Chen J

机构信息

Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

The State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences and School of Basic Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

出版信息

Oncogene. 2016 Jul 14;35(28):3647-57. doi: 10.1038/onc.2015.430. Epub 2015 Nov 9.

DOI:10.1038/onc.2015.430
PMID:26549028
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4947634/
Abstract

Long noncoding RNAs (lncRNAs) play important regulatory roles in a variety of diseases, including many tumors. However, the functional roles of these transcripts and mechanisms responsible for their deregulation in pancreatic ductal adenocarcinoma (PDAC) are not thoroughly understood. In this study, we discovered that lncRNA MIR31HG is markedly upregulated in PDAC. Knockdown of MIR31HG significantly suppressed PDAC cell growth, induced apoptosis and G1/S arrest, and inhibited invasion, whereas enhanced expression of MIR31HG had the opposite effects. Online database analysis tools showed that miR-193b could target MIR31HG and we found an inverse correlation between MIR31HG and miR-193b in PDAC specimens. Inhibition of miR-193b expression significantly upregulated the MIR31HG level, while overexpression of miR-193b suppressed MIR31HG's expression and function, suggesting that MIR31HG is negatively regulated by miR-193b. Moreover, using luciferase reporter and RIP assays, we provide evidence that miR-193b directly targeted MIR31HG by binding to two microRNA binding sites in the MIR31HG sequence. On the other hand, MIR31HG may act as an endogenous 'sponge' by competing for miR-193b binding to regulate the miRNA targets. Collectively, these results demonstrate that MIR31HG functions as an oncogenic lncRNA that promotes tumor progression, and miR-193b targets not only protein-coding genes but also the lncRNA, MIR31HG.

摘要

长链非编码RNA（lncRNAs）在包括许多肿瘤在内的多种疾病中发挥着重要的调节作用。然而，这些转录本在胰腺导管腺癌（PDAC）中的功能作用及其失调机制尚未完全明确。在本研究中，我们发现lncRNA MIR31HG在PDAC中显著上调。敲低MIR31HG可显著抑制PDAC细胞生长，诱导细胞凋亡和G1/S期阻滞，并抑制侵袭，而增强MIR31HG的表达则产生相反的效果。在线数据库分析工具显示miR-193b可靶向MIR31HG，并且我们在PDAC标本中发现MIR31HG与miR-193b呈负相关。抑制miR-193b的表达可显著上调MIR31HG水平，而miR-193b的过表达则抑制MIR31HG的表达和功能，这表明MIR31HG受miR-193b负调控。此外，通过荧光素酶报告基因和RIP实验，我们提供证据表明miR-193b通过结合MIR31HG序列中的两个微小RNA结合位点直接靶向MIR31HG。另一方面，MIR31HG可能通过竞争结合miR-193b来调节miRNA靶点，从而作为内源性“海绵”发挥作用。总之，这些结果表明MIR31HG作为一种致癌lncRNA促进肿瘤进展，并且miR-193b不仅靶向蛋白质编码基因，还靶向lncRNA MIR31HG。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02df/4947634/b2427289cdf6/onc2015430f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02df/4947634/58497dc64270/onc2015430f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02df/4947634/ac54a83d7f86/onc2015430f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02df/4947634/bf3aa8ca33d5/onc2015430f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02df/4947634/278434e159ec/onc2015430f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02df/4947634/51d3000de884/onc2015430f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02df/4947634/9eb6493538cf/onc2015430f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02df/4947634/b2427289cdf6/onc2015430f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02df/4947634/58497dc64270/onc2015430f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02df/4947634/ac54a83d7f86/onc2015430f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02df/4947634/bf3aa8ca33d5/onc2015430f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02df/4947634/278434e159ec/onc2015430f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02df/4947634/51d3000de884/onc2015430f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02df/4947634/9eb6493538cf/onc2015430f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02df/4947634/b2427289cdf6/onc2015430f7.jpg

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