Dataset Information

RWR-algorithm-based dissection of microRNA-506-3p and microRNA-140-5p as radiosensitive biomarkers in colorectal cancer.

ABSTRACT: Radiotherapy resistance is one of the main causes for treatment failure in colorectal cancer (CRC), and it is associated with the deregulation of certain microRNAs. In this study, we constructed the microRNA-mRNA network consisting of 2275 microRNAs and 7045 target genes, collected the known microRNAs related to CRC-radiosensitivity (CRCR) (n=18) as the seed nodes, and applied the algorithm of random walk with restart (RWR) to the network to identify novel CRCR-related microRNAs (n=263). In functional analysis, 263 novel microRNAs shared a high proportion of the same biological processes and pathways with the known microRNAs. In topological analysis of the sub-network of the 263 microRNAs and their targets, hsa-mir-506-3p and hsa-mir-140-5p were identified as network hub nodes. In plasma, radiosensitive patients had a higher expression level of hsa-mir-506-3p and hsa-mir-140-5p than radioresistant patients. In experimental validation, both hsa-mir-506-3p and hsa-mir-140-5p over-expression could obviously decrease the cell proliferation, survival rate and colonality in CRC cells after radiation. In conclusion, this study combined the novel network-based method with experimental validation, and identified two novel radiosensitive biomarkers of hsa-mir-506-3p and hsa-mir-140-5p in CRC.

SUBMITTER: Liao F

PROVIDER: S-EPMC7655152 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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RWR-algorithm-based dissection of microRNA-506-3p and microRNA-140-5p as radiosensitive biomarkers in colorectal cancer.

Liao Fei F Chen Xin X Peng Pailan P Dong Weiguo W

Aging 20201008 20

Radiotherapy resistance is one of the main causes for treatment failure in colorectal cancer (CRC), and it is associated with the deregulation of certain microRNAs. In this study, we constructed the microRNA-mRNA network consisting of 2275 microRNAs and 7045 target genes, collected the known microRNAs related to CRC-radiosensitivity (CRCR) (n=18) as the seed nodes, and applied the algorithm of random walk with restart (RWR) to the network to identify novel CRCR-related microRNAs (n=263). In func ...[more]

PMID: 33033230

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Project description:Background:MicroRNAs (miRNAs) in circulation have emerged as promising biomarkers. In this study, we aimed to identify a circulating miRNA signature for osteoarthritis (OA) patients and in combination with bioinformatics analysis to evaluate the utility of selected differentially expressed miRNAs in the serum as potential OA biomarkers. Methods:Serum samples were collected from 12 primary OA patients, and 12 healthy individuals were screened using the Agilent Human miRNA Microarray platform interrogating 2549 miRNAs. Receiver Operating Characteristic (ROC) curves were constructed to evaluate the diagnostic performance of the deregulated miRNAs. Expression levels of selected miRNAs were validated by quantitative real-time PCR (qRT-PCR) in all serum and in articular cartilage samples from OA patients (n =?12) and healthy individuals (n =?7). Bioinformatics analysis was used to investigate the involved pathways and target genes for the above miRNAs. Results:We identified 279 differentially expressed miRNAs in the serum of OA patients compared to controls. Two hundred and five miRNAs (73.5%) were upregulated and 74 (26.5%) downregulated. ROC analysis revealed that 77 miRNAs had area under the curve (AUC)?>?0.8 and p <?0.05. Bioinformatics analysis in the 77 miRNAs revealed that their target genes were involved in multiple signaling pathways associated with OA, among which FoxO, mTOR, Wnt, pI3K/akt, TGF-? signaling pathways, ECM-receptor interaction, and fatty acid biosynthesis. qRT-PCR validation in seven selected out of the 77 miRNAs revealed 3 significantly downregulated miRNAs (hsa-miR-33b-3p, hsa-miR-671-3p, and hsa-miR-140-3p) in the serum of OA patients, which were in silico predicted to be enriched in pathways involved in metabolic processes. Target-gene analysis of hsa-miR-140-3p, hsa-miR-33b-3p, and hsa-miR-671-3p revealed that InsR and IGFR1 were common targets of all three miRNAs, highlighting their involvement in regulation of metabolic processes that contribute to OA pathology. Hsa-miR-140-3p and hsa-miR-671-3p expression levels were consistently downregulated in articular cartilage of OA patients compared to healthy individuals. Conclusions:A serum miRNA signature was established for the first time using high density resolution miR-arrays in OA patients. We identified a three-miRNA signature, hsa-miR-140-3p, hsa-miR-671-3p, and hsa-miR-33b-3p, in the serum of OA patients, predicted to regulate metabolic processes, which could serve as a potential biomarker for the evaluation of OA risk and progression.

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Dataset Information

RWR-algorithm-based dissection of microRNA-506-3p and microRNA-140-5p as radiosensitive biomarkers in colorectal cancer.

Publications

RWR-algorithm-based dissection of microRNA-506-3p and microRNA-140-5p as radiosensitive biomarkers in colorectal cancer.

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