下调hsa-miR-135b-5p抑制结肠癌细胞增殖、迁移和侵袭

IF 1.4 4区 生物学 Q4 GENETICS & HEREDITY Genetics research Pub Date : 2022-01-01 DOI:10.1155/2022/2907554
Yunxin Zhang, Wentao Zhang, Wenlong Xia, Junwei Xia, Haishan Zhang
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引用次数: 0

摘要

结肠癌是最常见的胃肠道恶性肿瘤,约80%-90%的结肠癌为结肠腺癌(COADs)。本研究旨在筛选与COAD相关的关键microrna (mirna)。基于从数据集获得的基因表达Omnibus (GEO)和癌症基因组图谱,筛选COAD和邻近癌症样本之间的差异表达(DE) mirna。使用定量实时聚合酶链反应验证感兴趣的mirna。此外,观察hsa-miR-135b-5p对COAD细胞生物学行为的影响。为了获得hsa-miR-135b-5p的靶基因,我们对SW480细胞进行转录组测序,然后进行蛋白-蛋白相互作用(PPI)网络和hsa-miR-135b-5p靶基因调控网络的构建和预后分析。下调hsa-miR-135b-5p可显著抑制SW480细胞的增殖、迁移和侵袭,并显著促进凋亡(P FOXN2、NSA2、MYCBP、DIRAS2、DESI1和RAB33B具有预后意义(P FOXN2、NSA2、MYCBP、DIRAS2、DESI1和RAB33B在mir -135b-5p抑制剂和阴性对照组(P FOXN2、NSA2、MYCBP、DIRAS2、DESI1和RAB33B之间显著表达)。
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Downregulation of hsa-miR-135b-5p Inhibits Cell Proliferation, Migration, and Invasion in Colon Adenocarcinoma.

Colon cancer is the most common malignant tumor of the gastrointestinal tract, and approximately 80%-90% of colon cancers are colon adenocarcinomas (COADs). This study aimed to screen key microRNAs (miRNAs) associated with COAD. Differentially expressed (DE) miRNAs were screened between COAD and adjacent cancer samples based on the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas obtained from datasets. The miRNAs of interest were validated using quantitative real-time polymerase chain reaction. Moreover, the effects of hsa-miR-135b-5p on the biological behavior of COAD cells were observed. To obtain the target genes of hsa-miR-135b-5p, transcriptome sequencing of the SW480 cells was performed, followed by protein-protein interaction (PPI) network and hsa-miR-135b-5p-target gene regulatory network construction and prognostic analysis. Downregulation of hsa-miR-135b-5p significantly inhibited SW480 cell proliferation, migration, and invasion and significantly facilitated apoptosis (P < 0.05). A total of 3384 DEmRNAs were screened, and enrichment analysis showed that the upregulated mRNAs were enriched in 25 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and 326 Gene Ontology Biological Processes (GO-BPs) while the downregulated mRNAs were enriched in 20 KEGG pathways and 276 GO-BPs. A PPI network was then constructed, and H2BC14, H2BC3, and H4C11 had a higher degree. In addition, a total of 352 hsa-miR-135b-5p-gene regulatory relationships were identified. Prognostic analysis showed that FOXN2, NSA2, MYCBP, DIRAS2, DESI1, and RAB33B had prognostic significance (P < 0.05). In addition, the validation analysis results showed that FOXN2, NSA2, and DESI1 were significantly expressed between the miR-135b-5p-inhibitor and negative control groups (P < 0.05). Therefore, downregulation of hsa-miR-135b-5p inhibits cell proliferation, migration, and invasion in COAD, and carcinogenesis may function by targeting FOXN2, NSA2, MYCBP, DIRAS2, DESI1, and RAB33B.

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来源期刊
Genetics research
Genetics research 生物-遗传学
自引率
6.70%
发文量
74
审稿时长
>12 weeks
期刊介绍: Genetics Research is a key forum for original research on all aspects of human and animal genetics, reporting key findings on genomes, genes, mutations and molecular interactions, extending out to developmental, evolutionary, and population genetics as well as ethical, legal and social aspects. Our aim is to lead to a better understanding of genetic processes in health and disease. The journal focuses on the use of new technologies, such as next generation sequencing together with bioinformatics analysis, to produce increasingly detailed views of how genes function in tissues and how these genes perform, individually or collectively, in normal development and disease aetiology. The journal publishes original work, review articles, short papers, computational studies, and novel methods and techniques in research covering humans and well-established genetic organisms. Key subject areas include medical genetics, genomics, human evolutionary and population genetics, bioinformatics, genetics of complex traits, molecular and developmental genetics, Evo-Devo, quantitative and statistical genetics, behavioural genetics and environmental genetics. The breadth and quality of research make the journal an invaluable resource for medical geneticists, molecular biologists, bioinformaticians and researchers involved in genetic basis of diseases, evolutionary and developmental studies.
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