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miR-34a 调控的结直肠癌关键基因的鉴定。

Identification of Key Genes in Colorectal Cancer Regulated by miR-34a.

机构信息

Department of Anorectal Surgery, Tianjin Union Medical Center Nankai University Affiliated Hospital, Tianjin, China (mainland).

Department of General Surgery, Dagang Hospital, Tianjin, China (mainland).

出版信息

Med Sci Monit. 2017 Dec 3;23:5735-5743. doi: 10.12659/msm.904937.

DOI:10.12659/msm.904937
PMID:29197895
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5724350/
Abstract

BACKGROUND The aim of this study was to screen the molecular targets of miR-34a in colorectal cancer (CRC) and construct the regulatory network, to gain more insights to the pathogenesis of CRC. MATERIAL AND METHODS The microarray data of CRC samples and normal samples (GSE4988), as well as CRC samples transformed with miR-34a and non-transfected CRC samples (GSE7754), were downloaded from the Gene Expression Omnibus (GEO) database. The differently expressed genes (DEGs) were identified via the LIMMA package in R language. The Database for Annotation, Visualization and Integrated Discovery (DAVID) was used to identify significant Gene Ontology (GO) terms and pathways in DEGs. The targets of miR-34a were obtained via the miRWalk database, and then the overlaps between them were selected out to construct the regulatory network of miR-34a in CRC using the Cytoscape software. RESULTS A total of 392 DEGs were identified in CRC samples compared with normal samples, including 239 upregulated genes and 153 downregulated ones. These DEGs were enriched in 75 GO terms and one Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. At the same time, 332 DEGs (188 upregulated and 144 downregulated) were screened out between miR-34a transformed CRC and miR-34a non-transfected CRC samples and they were enriched in 20 GO terms and eight KEGG pathways. Six overlapped genes were identified in two DEGs groups. There were 1,668 targets of miR-34a obtained via the miRWalk database, among which 21 were identified differently expressed in miR-34a transformed CRC samples compared with miR-34a non-transfected CRC samples. Two regulatory networks of miR-34a in CRC within these two groups of overlapped genes were constructed respectively. CONCLUSIONS Pathways related to cell cycle, DNA replication, oocyte meiosis, and pyrimidine metabolism might play critical roles in the progression of CRC. Several genes such as SERPINE1, KLF4, SEMA4B, PPARG, CDC45, and KIAA0101 might be the targets of miR-34a and the potential therapeutic targets of CRC.

摘要

背景：本研究旨在筛选 miR-34a 在结直肠癌（CRC）中的分子靶点，并构建调控网络，以深入了解 CRC 的发病机制。

材料与方法：从基因表达综合数据库（GEO）下载 CRC 样本和正常样本的基因芯片数据（GSE4988），以及 miR-34a 转染的 CRC 样本和非转染的 CRC 样本（GSE7754）。使用 R 语言中的 LIMMA 包鉴定差异表达基因（DEGs）。使用数据库 for Annotation, Visualization and Integrated Discovery（DAVID）鉴定 DEGs 中的显著基因本体论（GO）术语和途径。通过 miRWalk 数据库获取 miR-34a 的靶基因，并从中选择重叠基因，使用 Cytoscape 软件构建 CRC 中 miR-34a 的调控网络。

结果：与正常样本相比，CRC 样本中共鉴定出 392 个 DEGs，其中 239 个上调基因和 153 个下调基因。这些 DEGs 富集于 75 个 GO 术语和 1 个京都基因与基因组百科全书（KEGG）途径。同时，在 miR-34a 转染的 CRC 样本和非转染的 miR-34a 的 CRC 样本之间筛选出 332 个 DEGs（188 个上调和 144 个下调），它们富集于 20 个 GO 术语和 8 个 KEGG 途径。在这两个 DEGs 组中，共鉴定出 6 个重叠基因。通过 miRWalk 数据库共获得 1668 个 miR-34a 的靶基因，其中 21 个在 miR-34a 转染的 CRC 样本与非转染的 miR-34a 的 CRC 样本之间差异表达。分别在这两个重叠基因组中构建了 miR-34a 在 CRC 中的两个调控网络。

结论：与细胞周期、DNA 复制、卵母细胞减数分裂和嘧啶代谢相关的途径可能在 CRC 的进展中发挥关键作用。SERPINE1、KLF4、SEMA4B、PPARG、CDC45 和 KIAA0101 等几个基因可能是 miR-34a 的靶基因，也是 CRC 的潜在治疗靶标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ddb/5724350/9e14a02b5b09/medscimonit-23-5735-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ddb/5724350/27ab5567d605/medscimonit-23-5735-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ddb/5724350/62dfb6372ee5/medscimonit-23-5735-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ddb/5724350/6d6ea66b92ac/medscimonit-23-5735-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ddb/5724350/9e14a02b5b09/medscimonit-23-5735-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ddb/5724350/27ab5567d605/medscimonit-23-5735-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ddb/5724350/62dfb6372ee5/medscimonit-23-5735-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ddb/5724350/6d6ea66b92ac/medscimonit-23-5735-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ddb/5724350/9e14a02b5b09/medscimonit-23-5735-g004.jpg

相似文献

[1]
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[2]
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[3]
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[4]
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[3]
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[4]
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World J Gastrointest Oncol. 2021-10-15

[5]
Long non-coding RNA NEAT1 promotes the malignancy of laryngeal squamous cell carcinoma by regulating the microRNA-204-5p/SEMA4B axis.

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[6]
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Bioengineered. 2020-12

[7]
Identification and verification of three key genes associated with survival and prognosis of COAD patients via integrated bioinformatics analysis.

Biosci Rep. 2020-9-30

[8]
Potential Prognostic and Diagnostic Values of CDC6, CDC45, ORC6 and SNHG7 in Colorectal Cancer.

Onco Targets Ther. 2019-12-31

[9]
TP53/miR-34a-associated signaling targets expression in human pancreatic cancer.

Aging (Albany NY). 2020-1-27

[10]
Exploring the Pharmacological Mechanism of the Herb Pair "HuangLian-GanJiang" against Colorectal Cancer Based on Network Pharmacology.

Evid Based Complement Alternat Med. 2019-11-29

本文引用的文献

[1]
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J Clin Oncol. 2013-6-3

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