Identification of Novel miRNAs, Targeting Genes, Signaling Pathway, and the Small Molecule for Overcoming Oxaliplatin Resistance of Metastatic Colorectal Cancer.
One of the globally common cancers is colorectal cancer (CRC). At present, a surgical approach remains a good option for CRC patients; however, 20% of surgically treated CRC patients experience metastasis. Currently, even the first-line used drug, oxaliplatin, remains inadequate for treating metasta...
| Publicado en: | BioMed Research International pp. 1 - 21 |
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| Autores principales: | , , , |
| Formato: | pictorial research tables/charts Journal Article |
| Publicado: |
Wiley-Blackwell
9/19/2022
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=159194752&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 159194752 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 23146133 FT2T jtl: BioMed Research International issn: 23146133 maglogo: N pubinfo: dt: 9/19/2022 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 159194752 159194752 159194752 10.1155/2022/3825760 159194752 ppf: 1 ppct: 20 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Identification of Novel miRNAs, Targeting Genes, Signaling Pathway, and the Small Molecule for Overcoming Oxaliplatin Resistance of Metastatic Colorectal Cancer. aug: au: Misbah, Md Kumar, Manoj Lee, Kuen-Huar Shen, Shing-Chuan affil: International Ph.D. Program in Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan sug: subj: MicroRNA Gene Expression Profiling Signal Transduction Small Molecules Oxaliplatin Therapeutic Use Drug Resistance, Neoplasm Colorectal Neoplasms Drug Therapy Neoplasm Metastasis Colorectal Neoplasms Prognosis Oxaliplatin Adverse Effects Neurotoxicity Syndromes Complications Cell Line, Tumor Cell Differentiation Proteins Metabolism Bioinformatics Disease-Free Survival Data Analysis Software Adipokines Human Descriptive Statistics ab: One of the globally common cancers is colorectal cancer (CRC). At present, a surgical approach remains a good option for CRC patients; however, 20% of surgically treated CRC patients experience metastasis. Currently, even the first-line used drug, oxaliplatin, remains inadequate for treating metastatic CRC, and its side effect of neurotoxicity is a major problem when treating CRC. The Gene Omnibus GSE42387 database contains gene expression profiles of parental and oxaliplatin-resistant LoVo cell lines. Differentially expressed genes (DEGs) between parental and oxaliplatin-resistance LoVo cells, protein-protein interactions (PPIs), and a pathway analysis were determined to identify overall biological changes by an online DAVID bioinformatics analysis. The ability of DEGs to predict overall survival (OS) and disease-free survival (DFS) was validated by the SPSS 22.0, using liver metastasis CRC patient samples of GSE41258. The bioinformatics web tools of the GEPIA, the Human Protein Atlas, WebGestalt, and TIMER platforms were used. In total, 218 DEGs were identified, among which 105 were downregulated and 113 were upregulated. After mapping the PPI networks and pathways, 60 DEGs were identified as hub genes (with high degrees). Six genes (TGFB1, CD36, THBS1, FABP1, PCK1, and IRS1) were involved with malaria, PPAR signaling, and the adipocytokine signaling pathway. High expressions of CD36 and PCK1 were associated with the poor survival of CRC patients in the GSE41258 database. We predicted specific micro (mi)RNAs that targeted the 3 ′ untranslated region (UTR) of PCK1 by using miRWalk. It was found that three miRNAs, viz., miR-7-5p, miR-20a-3p, and miR-636, may be upstream targets of those genes. High expression levels of miR-7-5p, miR-20a-3p, and miR-636 were associated with poor OS of CRC patients, and the small-molecule compound, mersalyl, is a promising drug for treating oxaliplatin-resistant CRC. In conclusion, miR-7-5p miR-20a-3p, and miR-636 targeted the PCK1 biomarker in the PPAR signaling pathway, which is involved in oxaliplatin-resistant CRC. Meanwhile, mersalyl was identified as a potential drug for overcoming oxaliplatin resistance in CRC. Our findings may provide novel directions and strategies for CRC therapies. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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