Dataset Information

Predicting Associations of miRNAs and Candidate Gastric Cancer Genes for Nanomedicine.

ABSTRACT: Nanoscale miRNAs regulate the synthesis of most human proteins involved in differentiation, proliferation, cell cycle, apoptosis, and other processes associated with the growth and the development of an organism. miRNAs also play a number of important roles in the development of gastric cancer. In this work, we studied the quantitative characteristics of miRNA interactions with 69 candidate gastric cancer genes using bioinformatics approaches. To this end, the MirTarget program was used, which determines the characteristics of miRNA binding to mRNA in the 5'UTR, CDS, and 3'UTR. Associations of miRNAs with alternative target genes and associations of genes with alternative miRNAs were established. The cluster organization of miRNA binding sites (BSs) in mRNA was revealed, leading to the emergence of miRNA competition for binding to the mRNA of a target gene. Groups of target genes with clusters of overlapping BSs include miR-5095, miR-619-5p, miR-1273 family, miR-466, ID01030.3p-miR, ID00436.3p-miR, miR-574-5p, and ID00470.5p-miR. In the defined associations of target genes and miRNAs, miRNA BSs are organized into clusters of multiple BSs, which facilitate the design and the development of a system of chips that can be used to control the state of miRNA and target genes associations in gastric cancer.

SUBMITTER: Akimniyazova A

PROVIDER: S-EPMC8000878 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Predicting Associations of miRNAs and Candidate Gastric Cancer Genes for Nanomedicine.

Akimniyazova Aigul A Pyrkova Anna A Uversky Vladimir V Ivashchenko Anatoliy A

Nanomaterials (Basel, Switzerland) 20210310 3

Nanoscale miRNAs regulate the synthesis of most human proteins involved in differentiation, proliferation, cell cycle, apoptosis, and other processes associated with the growth and the development of an organism. miRNAs also play a number of important roles in the development of gastric cancer. In this work, we studied the quantitative characteristics of miRNA interactions with 69 candidate gastric cancer genes using bioinformatics approaches. To this end, the MirTarget program was used, which d ...[more]

PMID: 33801990

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Project description:BackgroundThe TGFβ-signaling pathway plays an important role in the pathogenesis of colorectal cancer (CRC). Loss of function of several genes within this pathway, such as bone morphogenetic proteins (BMPs) have been seen as key events in CRC progression.MethodsIn this study we comprehensively evaluate differential gene expression (RNASeq) of 81 genes in the TGFβ-signaling pathway and evaluate how dysregulated genes are associated with miRNA expression (Agilent Human miRNA Microarray V19.0). We utilize paired carcinoma and normal tissue from 217 CRC cases. We evaluate the associations between differentially expressed genes and miRNAs and sex, age, disease stage, and survival months.ResultsThirteen genes were significantly downregulated and 14 were significantly upregulated after considering fold change (FC) of > 1.50 or < 0.67 and multiple comparison adjustment. Bone morphogenetic protein genes BMP5, BMP6, and BMP2 and growth differentiation factor GDF7 were downregulated. BMP4, BMP7, INHBA (Inhibin beta A), TGFBR1, TGFB2, TGIF1, TGIF2, and TFDP1 were upregulated. In general, genes with the greatest dysregulation, such as BMP5 (FC 0.17, BMP6 (FC 0.25), BMP2 (FC 0.32), CDKN2B (FC 0.32), MYC (FC 3.70), BMP7 (FC 4.17), and INHBA (FC 9.34) showed dysregulation in the majority of the population (84.3, 77.4, 81.1, 80.2, 82.0, 51.2, and 75.1% respectively). Four genes, TGFBR2, ID4, ID1, and PITX2, were un-associated or slightly upregulated in microsatellite-stable (MSS) tumors while downregulated in microsatellite-unstable (MSI) tumors. Eight dysregulated genes were associated with miRNA differential expression. E2F5 and THBS1 were associated with one or two miRNAs; RBL1, TGFBR1, TGIF2, and INHBA were associated with seven or more miRNAs with multiple seed-region matches. Evaluation of the joint effects of mRNA:miRNA identified interactions that were stronger in more advanced disease stages and varied by survival months.ConclusionThese data support an interaction between miRNAs and genes in the TGFβ-signaling pathway in association with CRC risk. These interactions are associated with unique clinical characteristics that may provide targets for further investigations.

Dataset Information

Predicting Associations of miRNAs and Candidate Gastric Cancer Genes for Nanomedicine.

Publications

Predicting Associations of miRNAs and Candidate Gastric Cancer Genes for Nanomedicine.

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