{"title":"下调hsa-miR-135b-5p抑制结肠癌细胞增殖、迁移和侵袭","authors":"Yunxin Zhang, Wentao Zhang, Wenlong Xia, Junwei Xia, Haishan Zhang","doi":"10.1155/2022/2907554","DOIUrl":null,"url":null,"abstract":"<p><p>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 (<i>P</i> < 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 <i>FOXN2</i>, <i>NSA2</i>, <i>MYCBP</i>, <i>DIRAS2</i>, <i>DESI1</i>, and <i>RAB33B</i> had prognostic significance (<i>P</i> < 0.05). In addition, the validation analysis results showed that <i>FOXN2</i>, <i>NSA2</i>, and <i>DESI1</i> were significantly expressed between the miR-135b-5p-inhibitor and negative control groups (<i>P</i> < 0.05). Therefore, downregulation of hsa-miR-135b-5p inhibits cell proliferation, migration, and invasion in COAD, and carcinogenesis may function by targeting <i>FOXN2</i>, <i>NSA2</i>, <i>MYCBP</i>, <i>DIRAS2</i>, <i>DESI1</i>, and <i>RAB33B</i>.</p>","PeriodicalId":12778,"journal":{"name":"Genetics research","volume":"2022 ","pages":"2907554"},"PeriodicalIF":1.4000,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9640266/pdf/","citationCount":"0","resultStr":"{\"title\":\"Downregulation of hsa-miR-135b-5p Inhibits Cell Proliferation, Migration, and Invasion in Colon Adenocarcinoma.\",\"authors\":\"Yunxin Zhang, Wentao Zhang, Wenlong Xia, Junwei Xia, Haishan Zhang\",\"doi\":\"10.1155/2022/2907554\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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 (<i>P</i> < 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 <i>FOXN2</i>, <i>NSA2</i>, <i>MYCBP</i>, <i>DIRAS2</i>, <i>DESI1</i>, and <i>RAB33B</i> had prognostic significance (<i>P</i> < 0.05). In addition, the validation analysis results showed that <i>FOXN2</i>, <i>NSA2</i>, and <i>DESI1</i> were significantly expressed between the miR-135b-5p-inhibitor and negative control groups (<i>P</i> < 0.05). Therefore, downregulation of hsa-miR-135b-5p inhibits cell proliferation, migration, and invasion in COAD, and carcinogenesis may function by targeting <i>FOXN2</i>, <i>NSA2</i>, <i>MYCBP</i>, <i>DIRAS2</i>, <i>DESI1</i>, and <i>RAB33B</i>.</p>\",\"PeriodicalId\":12778,\"journal\":{\"name\":\"Genetics research\",\"volume\":\"2022 \",\"pages\":\"2907554\"},\"PeriodicalIF\":1.4000,\"publicationDate\":\"2022-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9640266/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Genetics research\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1155/2022/2907554\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Genetics research","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1155/2022/2907554","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
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.
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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