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通过RNA测序分析胰腺导管腺癌的微小RNA表达特征：该簇的抗肿瘤功能

The microRNA expression signature of pancreatic ductal adenocarcinoma by RNA sequencing: anti-tumour functions of the cluster.

作者信息

Yonemori Keiichi, Seki Naohiko, Idichi Tetsuya, Kurahara Hiroshi, Osako Yusaku, Koshizuka Keiichi, Arai Takayuki, Okato Atsushi, Kita Yoshiaki, Arigami Takaaki, Mataki Yuko, Kijima Yuko, Maemura Kosei, Natsugoe Shoji

机构信息

Department of Digestive Surgery, Breast and Thyroid Surgery, Graduate School of Medical Sciences, Kagoshima University, Sakuragaoka, Kagoshima 890-8520, Japan.

Department of Functional Genomics, Chiba University Graduate School of Medicine, Chuo-ku, Chiba 260-8670, Japan.

出版信息

Oncotarget. 2017 Jul 26;8(41):70097-70115. doi: 10.18632/oncotarget.19591. eCollection 2017 Sep 19.

DOI:10.18632/oncotarget.19591
PMID:29050264
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5642539/
Abstract

We analysed the RNA sequence-based microRNA (miRNA) signature of pancreatic ductal adenocarcinoma (PDAC). Aberrantly expressed miRNAs were successfully identified in this signature. Using the PDAC signature, we focused on 4 clustered miRNAs, , , and on human chromosome 2p16.1. All members of the cluster were significantly reduced in PDAC specimens. Ectopic expression of these miRNAs suppressed cancer cell aggressiveness, suggesting cluster as anti-tumour miRNAs in PDAC cells. The impact of (passenger strand of pre-) on cancer cells is still ambiguous. Forkhead box Q1 () was directly regulated by and overexpression of was confirmed in clinical specimens. High expression of predicted a shorter survival of patients with PDAC by Kaplan-Meier analysis. Loss-of-function assays showed that cancer cell migration and invasion activities were significantly reduced by si transfectants. We investigated pathways downstream from by using genome-wide gene expression analysis. Identification of the -mediated network in PDAC should enhance understanding of PDAC aggressiveness at the molecular level.

摘要

我们分析了胰腺导管腺癌（PDAC）基于RNA序列的微小RNA（miRNA）特征。在该特征中成功鉴定出异常表达的miRNA。利用PDAC特征，我们聚焦于人类2号染色体p16.1上的4个成簇miRNA，即 、 、 和 。 簇的所有成员在PDAC标本中均显著降低。这些miRNA的异位表达抑制了癌细胞的侵袭性，表明 簇在PDAC细胞中作为抗肿瘤miRNA。 （前体 的过客链）对癌细胞的影响仍不明确。叉头框Q1（ ）受 直接调控，且在临床标本中证实了 的过表达。通过Kaplan-Meier分析， 的高表达预示着PDAC患者生存期较短。功能丧失实验表明，si转染剂可显著降低癌细胞的迁移和侵袭活性。我们通过全基因组基因表达分析研究了 下游的信号通路。鉴定PDAC中 -介导的网络应能增强对PDAC在分子水平侵袭性的理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a370/5642539/cff83875f5b2/oncotarget-08-70097-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a370/5642539/db1dbf107f50/oncotarget-08-70097-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a370/5642539/d3b67f9ffb91/oncotarget-08-70097-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a370/5642539/e9e1630c2d81/oncotarget-08-70097-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a370/5642539/ec56392246ab/oncotarget-08-70097-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a370/5642539/0df48f9a0c28/oncotarget-08-70097-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a370/5642539/01bff2eb9d44/oncotarget-08-70097-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a370/5642539/cff83875f5b2/oncotarget-08-70097-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a370/5642539/db1dbf107f50/oncotarget-08-70097-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a370/5642539/d3b67f9ffb91/oncotarget-08-70097-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a370/5642539/e9e1630c2d81/oncotarget-08-70097-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a370/5642539/ec56392246ab/oncotarget-08-70097-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a370/5642539/0df48f9a0c28/oncotarget-08-70097-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a370/5642539/01bff2eb9d44/oncotarget-08-70097-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a370/5642539/cff83875f5b2/oncotarget-08-70097-g007.jpg

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