Dataset Information

LncRNA, a novel target biomolecule, is involved in the progression of colorectal cancer.

ABSTRACT: Colorectal cancer is one of the most commonly diagnosed malignancies among males and females worldwide. Although China is a country with a low incidence of colorectal cancer, with the improvement of China's economy and lifestyle changes, the incidence rate in China has generally increased in recent years, and the morbidity and mortality of colorectal cancer rank fifth among those of all malignant tumours. Furthermore, despite recent improvements in screening strategies and treatments for colorectal cancer, the prognosis of advanced colorectal cancer is still poor, mainly due to the recurrence or distant metastasis of this disease. Thus, colorectal cancer still seriously threatens the health and life of people and is a major public health problem worthy of further study. Recently, accumulating evidence has revealed that colorectal carcinogenesis might be a multistep process driven by progressive genetic abnormalities, including changes in lncRNA expression. Moreover, a large number of studies have discovered and studied the abnormal expression of lncRNAs in colorectal cancer, providing a promising target for the diagnosis and treatment of colorectal cancer, which will promote human understanding of the pathogenesis of colorectal cancer and improve diagnosis and treatment. Therefore, in the present review, we mainly summarize the present status of colorectal cancer, the characteristics, functions and clinical perspectives of lncRNAs, and the current therapeutic methods used for colorectal cancer, especially the application of lncRNAs in the treatment of colorectal cancer. It is hoped that this review will give readers a new understanding of the roles of lncRNAs in colorectal cancer.

SUBMITTER: Sun W

PROVIDER: S-EPMC6895445 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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LncRNA, a novel target biomolecule, is involved in the progression of colorectal cancer.

Sun Weihong W Ren Shaoshao S Li Ran R Zhang Qingshan Q Song Haiping H

American journal of cancer research 20191101 11

Colorectal cancer is one of the most commonly diagnosed malignancies among males and females worldwide. Although China is a country with a low incidence of colorectal cancer, with the improvement of China's economy and lifestyle changes, the incidence rate in China has generally increased in recent years, and the morbidity and mortality of colorectal cancer rank fifth among those of all malignant tumours. Furthermore, despite recent improvements in screening strategies and treatments for colorec ...[more]

PMID: 31815050

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Project description:BackgroundAcquired drug resistance to the chemotherapeutic drug irinotecan (the active metabolite of which is SN-38) is one of the significant obstacles in the treatment of advanced colorectal cancer (CRC). The molecular mechanism or targets mediating irinotecan resistance are still unclear. It is urgent to find the irinotecan response biomarkers to improve CRC patients' therapy.MethodsGenetic Omnibus Database GSE42387 which contained the gene expression profiles of parental and irinotecan-resistant HCT-116 cell lines was used. Differentially expressed genes (DEGs) between parental and irinotecan-resistant cells, protein-protein interactions (PPIs), gene ontologies (GOs) and pathway analysis were performed to identify the overall biological changes. The most common DEGs in the PPIs, GOs and pathways were identified and were validated clinically by their ability to predict overall survival and disease free survival. The gene-gene expression correlation and gene-resistance correlation was also evaluated in CRC patients using The Cancer Genomic Atlas data (TCGA).ResultsThe 135 DEGs were identified of which 36 were upregulated and 99 were down regulated. After mapping the PPI networks, the GOs and the pathways, nine genes (GNAS, PRKACB, MECOM, PLA2G4C, BMP6, BDNF, DLG4, FGF2 and FGF9) were found to be commonly enriched. Signal transduction was the most significant GO and MAPK pathway was the most significant pathway. The five genes (FGF2, FGF9, PRKACB, MECOM and PLA2G4C) in the MAPK pathway were all contained in the signal transduction and the levels of those genes were upregulated. The FGF2, FGF9 and MECOM expression were highly associated with CRC patients' survival rate but not PRKACB and PLA2G4C. In addition, FGF9 was also associated with irinotecan resistance and poor disease free survival. FGF2, FGF9 and PRKACB were positively correlated with each other while MECOM correlated positively with FGF9 and PLA2G4C, and correlated negatively with FGF2 and PRKACB after doing gene-gene expression correlation.ConclusionTargeting the MAPK signal transduction pathway through the targeting of the FGF2, FGF9, MECOM, PLA2G4C and PRKACB might increase tumor responsiveness to irinotecan treatment.

Project description:Bevacizumab combined with cytotoxic chemotherapy is the backbone of metastatic colorectal cancer (mCRC) therapy; however, its treatment efficacy is hampered by therapeutic resistance. Therefore, understanding the mechanisms underlying bevacizumab resistance is crucial to increasing the therapeutic efficacy of bevacizumab. The Gene Expression Omnibus (GEO) database (dataset, GSE86525) was used to identify the key genes and pathways involved in bevacizumab-resistant mCRC. The GEO2R web tool was used to identify differentially expressed genes (DEGs). Functional and pathway enrichment analyses of the DEGs were performed using the Database for Annotation, Visualization, and Integrated Discovery(DAVID). Protein-protein interaction (PPI) networks were established using the Search Tool for the Retrieval of Interacting Genes/Proteins database(STRING) and visualized using Cytoscape software. A total of 124 DEGs were obtained, 57 of which upregulated and 67 were downregulated. PPI network analysis showed that seven upregulated genes and nine downregulated genes exhibited high PPI degrees. In the functional enrichment, the DEGs were mainly enriched in negative regulation of phosphate metabolic process and positive regulation of cell cycle process gene ontologies (GOs); the enriched pathways were the phosphoinositide 3-kinase-serine/threonine kinase signaling pathway, bladder cancer, and microRNAs in cancer. Cyclin-dependent kinase inhibitor 1A(CDKN1A), toll-like receptor 4 (TLR4), CD19 molecule (CD19), breast cancer 1, early onset (BRCA1), platelet-derived growth factor subunit A (PDGFA), and matrix metallopeptidase 1 (MMP1) were the DEGs involved in the pathways and the PPIs. The clinical validation of the DEGs in mCRC (TNM clinical stages 3 and 4) revealed that high PDGFA expression levels were associated with poor overall survival, whereas high BRCA1 and MMP1 expression levels were associated with favorable progress free survival(PFS). The identified genes and pathways can be potential targets and predictors of therapeutic resistance and prognosis in bevacizumab-treated patients with mCRC.

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LncRNA, a novel target biomolecule, is involved in the progression of colorectal cancer.

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LncRNA, a novel target biomolecule, is involved in the progression of colorectal cancer.

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