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环状泛素相关蛋白2介导的竞争性内源性RNA网络调控胰腺腺癌的肿瘤发生。

CircUBAP2-mediated competing endogenous RNA network modulates tumorigenesis in pancreatic adenocarcinoma.

作者信息

Zhao Rongjie, Ni Junjie, Lu Si, Jiang Sujing, You Liangkun, Liu Hao, Shou Jiawei, Zhai Chongya, Zhang Wei, Shao Shengpeng, Yang Xinmei, Pan Hongming, Han Weidong

机构信息

Department of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou 310000, Zhejiang, China.

The First Clinical College, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, China.

出版信息

Aging (Albany NY). 2019 Oct 4;11(19):8484-8501. doi: 10.18632/aging.102334.

DOI:10.18632/aging.102334
PMID:31584877
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6814619/
Abstract

We investigated the role of the competing endogenous RNA (ceRNA) network in the development and progression of pancreatic adenocarcinoma (PAAD). We analyzed the expression profiles of PAAD and normal pancreatic tissues from multiple GEO databases and identified 457 differentially expressed circular RNAs (DEcircRNAs), 19 microRNAs (DEmiRNAs) and 1993 mRNAs (DEmRNAs). We constructed a ceRNA network consisting of 4 DEcircRNAs, 3 DEmiRNAs and 149 DEmRNAs that regulates the NF-kappa B, PI3K-Akt, and Wnt signaling pathways. We then identified and validated five hub genes, , , , and , which are overexpressed in PAAD tissues. The expression of , , and in PAAD was regulated by and . The expression of and correlated with the levels of M2 macrophages, T-regulatory cells (Tregs) and exhausted T cells in the PAAD tissues. The expression of and ZEB1 positively correlated with the expression of and . This suggests that and proteins inhibit antigen presentation and promote immune escape mechanisms in PAAD cells. In summary, our data suggest that the -mediated ceRNA network modulates PAAD by regulating the infiltration and function of immune cells.

摘要

我们研究了竞争性内源性RNA（ceRNA）网络在胰腺腺癌（PAAD）发生发展过程中的作用。我们分析了来自多个GEO数据库的PAAD组织和正常胰腺组织的表达谱，鉴定出457个差异表达的环状RNA（DEcircRNAs）、19个微小RNA（DEmiRNAs）和1993个信使RNA（DEmRNAs）。我们构建了一个由4个DEcircRNAs、3个DEmiRNAs和149个DEmRNAs组成的ceRNA网络，该网络调控核因子κB、PI3K-Akt和Wnt信号通路。然后我们鉴定并验证了5个在PAAD组织中过表达的枢纽基因，即 、 、 、 和 。PAAD中 、 、 和 的表达受 和 的调控。 和 的表达与PAAD组织中M2巨噬细胞、调节性T细胞（Tregs）和耗竭性T细胞的水平相关。 和ZEB1的表达与 和 的表达呈正相关。这表明 和 蛋白抑制PAAD细胞中的抗原呈递并促进免疫逃逸机制。总之，我们的数据表明， 介导的ceRNA网络通过调节免疫细胞的浸润和功能来调节PAAD。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16b3/6814619/2c2a4fe9efe9/aging-11-102334-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16b3/6814619/2925cdfe4b91/aging-11-102334-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16b3/6814619/65d100002ad3/aging-11-102334-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16b3/6814619/59c0c2905e9c/aging-11-102334-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16b3/6814619/3a1dd9520f08/aging-11-102334-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16b3/6814619/a9ee49edefc6/aging-11-102334-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16b3/6814619/4ab52005150d/aging-11-102334-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16b3/6814619/c71c08c1cef6/aging-11-102334-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16b3/6814619/7f02f805b158/aging-11-102334-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16b3/6814619/2c2a4fe9efe9/aging-11-102334-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16b3/6814619/2925cdfe4b91/aging-11-102334-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16b3/6814619/65d100002ad3/aging-11-102334-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16b3/6814619/59c0c2905e9c/aging-11-102334-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16b3/6814619/3a1dd9520f08/aging-11-102334-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16b3/6814619/a9ee49edefc6/aging-11-102334-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16b3/6814619/4ab52005150d/aging-11-102334-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16b3/6814619/c71c08c1cef6/aging-11-102334-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16b3/6814619/7f02f805b158/aging-11-102334-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16b3/6814619/2c2a4fe9efe9/aging-11-102334-g009.jpg

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