Computational Analysis of miRNA and their Gene Targets Significantly Involved in Colorectal Cancer Progression

Kandhavelu, Jeyalakshmi; Kumar, Santosh; Khan, Amber; Omar, Aadilah; Ruff, Paul; Penny, Clement

doi:10.2174/2211536607666180803100246

Cited by 15 publications

(8 citation statements)

References 33 publications

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“…Xie L et al [44] adopted high-throughput sequencing from peripheral blood mononuclear cells in small cell osteosarcoma and detected dysregulation of miR-221-3p. Kandhavelu J et al [45] found that miR-424-5p was associated with 10 biomarkers of colon carcinoma, while only two of them, including microtubuleassociated protein-2 (MAP2) and cyclin gene (CCN) D1, were experimentally validated. Liang Y et al [46] identi ed miR-424-5p as a potential prognostic biomarker for gastric cancer.…”

Section: Discussionmentioning

confidence: 99%

An immune-related microRNA signature prognostic model for pancreatic carcinoma and association with immune microenvironment

Shen

Pan

et al. 2022

Preprint

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Objective To establish a prognostic model based on immune-related microRNA (miRNA) for pancreatic carcinoma. Methods Weighted correlation network analysis (WGCNA) was performed using the "WGCNA" package to find the key module genes involved in pancreatic carcinoma. Spearman correlation analysis was conducted to screen immune-related miRNAs. Uni- and multi-variate COX regression analyses were carried out to identify miRNAs prognostic for overall survival (OS) of pancreatic carcinoma, which were then combined to generate a prognostic model. Kaplan-Meier survival analysis, receiver operating characteristic (ROC) analysis, distribution plot of survival status in patients and regression analysis were collectively performed to study the accuracy of the model in prognosis. Target genes of the miRNAs in the model were intersected with the key module genes, and a miRNA-mRNA network was generated and visualized by Cytoscape3.8.0. TIMER analysis was conducted to study the abundance of immune infiltrates in tumor microenvironment of pancreatic carcinoma. Expression levels of immune checkpoint genes in subgroups stratified by the model were compared by Wilcoxon test. Gene Set Enrichment Analysis (GSEA) was performed to analyze the enriched signaling pathways between subgroups. Results Differential analysis revealed 1,826 genes differentially up-regulated in pancreatic carcinoma and 1,276 genes differentially down-regulated. A total of 700 immune-related miRNAs were obtained, of which 7 miRNAs were significantly associated with OS of patients and used to establish a prognostic model with accurate predictive performance. There were 99 mRNAs overlapped from the 318 target genes of the 7 miRNAs and the key modules genes analyzed by WGCNA. Patient samples were categorized as high or low risk according to the prognostic model, which were significantly associated with dendritic cell infiltration and expression of immune checkpoint genes (TNFSF9, TNFRSF9, KIR3DL1, HAVCR2, CD276 and CD80). GSEA showed remarkably enriched signaling pathways in the two subgroups. Conclusion This study identified an immune-related 7-miRNA based prognostic model for pancreatic carcinoma, which could be used as a reliable tool for prognosis.

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Section: Discussionmentioning

confidence: 99%

An immune-related microRNA signature prognostic model for pancreatic carcinoma and association with immune microenvironment

Shen

Pan

et al. 2022

Preprint

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“…Therefore, reproducible biomarkers are needed to predict the survival of patients with HCC at clinical settings. Based on bioinformatic studies, extensive evidence has been theoretically investigated to show that abundant target genes were regulated by miRNAs, which virtually involves in every process of malignant tumors pathway regulation, therapeutic strategy, and prognosis [26][27][28][29]. In particular, in the process of tumorigenesis and development, a large number of miRNAs play different roles as prognostic biomarkers, including lung cancer [30], breast cancer [31], colorectal cancer [32], prostate cancer [33], gastric cancer [34], and pancreatic cancer [35].…”

Section: Discussionmentioning

confidence: 99%

Construction and validation of a three-microRNA signature as prognostic biomarker in patients with hepatocellular carcinoma

Zhang¹,

Ma²,

Zhai³

et al. 2021

Int. J. Med. Sci.

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Hepatocellular carcinoma (HCC), a common type of primary liver cancer, is one of the most aggressive malignant tumors worldwide. Although overall survival (OS) rates for HCC has significantly improved in recent years, however, the exact predictive value of microRNA (miRNA) for the prognosis of HCC has not yet been recognized. Here, we aimed to identify potential prognostic miRNAs involved in HCC by bioinformatics analysis and validated expression levels through quantitative polymerase chain reaction (qPCR) and GEO database. The RNA expression profiles and corresponding clinical information of HCC were available from The Cancer Genome Atlas (TCGA) datasets. Differentially expression and standardization analysis of miRNAs, Kaplan-Meier curve and time dependent ROC curve were performed by using R tools. Differentially expressed miRNAs (DEmiRNAs) and clinical parameters involved in the OS of HCC were confirmed by Cox regression models. And functional enrichment analysis was used to establish functions of the targeted genes of DEmiRNAs. A total of 300 DEmiRNAs were significantly related with HCC, of which 40 were down-regulated and 260 were up-regulated. A total of 344 patients with DEmiRNAs, status, overall survival (OS) time were randomized into training group (172) and test group (172). Multivariate Cox regression analyses revealed that 3 miRNA (hsa-miR-139-3p, hsa-miR-760, hsa-miR-7-5p) had independent prognostic significance for the OS of HCC in both training and test group. Moreover, according to Kaplan Meier analysis, the OS of HCC patients with high-risk score was shorter in validation and entire series. The time dependent ROC curve demonstrated high accuracy of the signature for OS. Besides, target genes of three miRNAs were analyzed by functional enrichment analysis and 20 genes associated with OS were verified by using Kaplan-Meier method. Compared with normal and benign group, the relative expression level of hsa-miR-139-3p was significantly decreased, while hsa-miR-7-5p and hsa-miR-760 were distinctly increased in the plasma of HCC patients. The same results were observed in the independent cohort. Collectively, our research suggested that three-miRNA signature could serve as an independent prognostic indicator for HCC patients.

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“…27 The target genes of miRNAs were also explored by bioinformatics approaches, which showed that they were Clinical Medicine Insights: Oncology involved in colorectal cancer progression. 28 At the same time, because of their central role in the regulation of the signaling pathways in which their target genes are involved, modulating miRNA expression for cancer therapy is currently under investigation. The therapeutic potential of miRNA is attracting a great deal of interest as potential targets for cancer treatment are identified in increasing numbers of studies.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-19b Downregulates NR3C1 and Enhances Oxaliplatin Chemoresistance in Colon Cancer via the PI3K/AKT/mTOR Pathway

Han

Chao

Wang

et al. 2021

Clin Med Insights Oncol

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Background: Identifying the genes and signaling pathways related to chemoresistance might facilitate the development of novel therapeutic strategies for colon cancer. In this study, we aimed to investigate the biological functions and underlying mechanisms of action of miR-19b and NR3C1, as well as their effects on chemosensitivity to oxaliplatin and prognosis of colon cancer patients. Methods: Reverse transcription–polymerase chain reaction (RT-PCR), Western blotting, and immunohistochemical staining were used to analyze the expression of miR-19b and NR3C1. Dual firefly luciferase reporter gene analysis was used to identify miR-19b target genes. Associations of miR-19b and NR3C1 with survival were estimated by the Kaplan–Meier method and Cox regression analyses. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometric analysis were used to measure cell viability, cytotoxicity, cell cycle phase, and apoptosis, respectively. The effect of miR-19b on cell proliferation was investigated in vivo. Results: The miR-19b was overexpressed and NR3C1 was decreased in colon cancer tissue and cell lines (SW480 and DLD-1). The miR-19b inhibition and NR3C1 overexpression inhibited cell proliferation, and induced G1/S cell cycle blockade, apoptosis, and chemosensitivity to oxaliplatin in vitro. The miR-19b inhibition suppressed subcutaneous tumorigenesis in vivo. Increased miR-19b and decreased NR3C1 in colon cancer were correlated with poor prognosis. In addition, our results confirmed NR3C1 was directly targeted by miR-19b. Thus, miR-19b might inhibit apoptosis and enhance oxaliplatin chemoresistance via the PI3K/AKT/mTOR pathway. Conclusions: Our study revealed that miR-19b promotes cell survival and chemoresistance to oxaliplatin via the PI3K/AKT/mTOR pathway by downregulating NR3C1 in colon cancer. miR-19b and NR3C1 might be potential intervention targets for chemoresistance of colon cancer.

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Computational Analysis of miRNA and their Gene Targets Significantly Involved in Colorectal Cancer Progression

Abstract: These miRNAs and their targets require further evaluation for a better understanding of their associations, ultimately with the potential to develop novel therapeutic targets.

Cited by 15 publications

References 33 publications

An immune-related microRNA signature prognostic model for pancreatic carcinoma and association with immune microenvironment

An immune-related microRNA signature prognostic model for pancreatic carcinoma and association with immune microenvironment

Construction and validation of a three-microRNA signature as prognostic biomarker in patients with hepatocellular carcinoma

MicroRNA-19b Downregulates NR3C1 and Enhances Oxaliplatin Chemoresistance in Colon Cancer via the PI3K/AKT/mTOR Pathway

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