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The modularity and dynamicity of miRNA-mRNA interactions in high-grade serous ovarian carcinomas and the prognostic implication.

作者信息

Zhang Wensheng, Edwards Andrea, Fan Wei, Flemington Erik K, Zhang Kun

机构信息

Department of Computer Science, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, LA 70125, United States.

Big Data Lab, Baidu Research, 1195 Bordeaux Dr., Sunnyvale, CA 94089, United States.

出版信息

Comput Biol Chem. 2016 Aug;63:3-14. doi: 10.1016/j.compbiolchem.2016.02.005. Epub 2016 Feb 27.


DOI:10.1016/j.compbiolchem.2016.02.005
PMID:26949157
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4976019/
Abstract

Ovarian carcinoma is the fifth-leading cause of cancer death among women in the United States. Major reasons for this persistent mortality include the poor understanding of the underlying biology and a lack of reliable biomarkers. Previous studies have shown that aberrantly expressed MicroRNAs (miRNAs) are involved in carcinogenesis and tumor progression by post-transcriptionally regulating gene expression. However, the interference of miRNAs in tumorigenesis is quite complicated and far from being fully understood. In this work, by an integrative analysis of mRNA expression, miRNA expression and clinical data published by The Cancer Genome Atlas (TCGA), we studied the modularity and dynamicity of miRNA-mRNA interactions and the prognostic implications in high-grade serous ovarian carcinomas. With the top transcriptional correlations (Bonferroni-adjusted p-value<0.01) as inputs, we identified five miRNA-mRNA module pairs (MPs), each of which included one positive-connection (correlation) module and one negative-connection (correlation) module. The number of miRNAs or mRNAs in each module varied from 3 to 7 or from 2 to 873. Among the four major negative-connection modules, three fit well with the widely accepted miRNA-mediated post-transcriptional regulation theory. These modules were enriched with the genes relevant to cell cycle and immune response. Moreover, we proposed two novel algorithms to reveal the group or sample specific dynamic regulations between these two RNA classes. The obtained miRNA-mRNA dynamic network contains 3350 interactions captured across different cancer progression stages or tumor grades. We found that those dynamic interactions tended to concentrate on a few miRNAs (e.g. miRNA-936), and were more likely present on the miRNA-mRNA pairs outside the discovered modules. In addition, we also pinpointed a robust prognostic signature consisting of 56 modular protein-coding genes, whose co-expression patterns were predictive for the survival time of ovarian cancer patients in multiple independent cohorts.

摘要

相似文献

[1]
The modularity and dynamicity of miRNA-mRNA interactions in high-grade serous ovarian carcinomas and the prognostic implication.

Comput Biol Chem. 2016-8

[2]
Integrated microRNA and mRNA signatures associated with overall survival in epithelial ovarian cancer.

PLoS One. 2021

[3]
miRNA-mRNA correlation-network modules in human prostate cancer and the differences between primary and metastatic tumor subtypes.

PLoS One. 2012-6-29

[4]
Integrated analyses of microRNAs demonstrate their widespread influence on gene expression in high-grade serous ovarian carcinoma.

PLoS One. 2012-3-29

[5]
Identification of common oncogenic and early developmental pathways in the ovarian carcinomas controlling by distinct prognostically significant microRNA subsets.

BMC Genomics. 2017-10-3

[6]
Characterization of microRNA expression in serous ovarian carcinoma.

Int J Mol Med. 2014-8

[7]
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[8]
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[9]
Gene-microRNA network module analysis for ovarian cancer.

BMC Syst Biol. 2016-12-23

[10]
Identification of miRNA-mRNA regulatory modules by exploring collective group relationships.

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引用本文的文献

[1]
Integrated microRNA and mRNA signatures associated with overall survival in epithelial ovarian cancer.

PLoS One. 2021

[2]
Driver gene mutations based clustering of tumors: methods and applications.

Bioinformatics. 2018-7-1

本文引用的文献

[1]
Cancer statistics, 2014.

CA Cancer J Clin. 2014-1-7

[2]
A new algorithm for integrated analysis of miRNA-mRNA interactions based on individual classification reveals insights into bladder cancer.

PLoS One. 2013-5-24

[3]
The shaping and functional consequences of the microRNA landscape in breast cancer.

Nature. 2013-5-5

[4]
The impact of quantile and rank normalization procedures on the testing power of gene differential expression analysis.

BMC Bioinformatics. 2013-4-11

[5]
Network-based survival analysis reveals subnetwork signatures for predicting outcomes of ovarian cancer treatment.

PLoS Comput Biol. 2013-3-21

[6]
Transcription factor-microRNA-target gene networks associated with ovarian cancer survival and recurrence.

PLoS One. 2013-3-12

[7]
Downregulation of miR-145 associated with cancer progression and VEGF transcriptional activation by targeting N-RAS and IRS1.

Biochim Biophys Acta. 2013-2

[8]
miRNA-mRNA correlation-network modules in human prostate cancer and the differences between primary and metastatic tumor subtypes.

PLoS One. 2012-6-29

[9]
MAGIA²: from miRNA and genes expression data integrative analysis to microRNA-transcription factor mixed regulatory circuits (2012 update).

Nucleic Acids Res. 2012-5-21

[10]
Mab21l2 is essential for embryonic heart and liver development.

PLoS One. 2012-3-8

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