title: Enrichment Analysis Identifies Functional MicroRNA-Disease Associations in Humans.
abstract: Substantial evidence has shown that microRNAs (miRNAs) may be causally linked to the occurrence and progression of human diseases. Herein, we conducted an enrichment analysis to identify potential functional miRNA-disease associations (MDAs) in humans by integrating currently known biological data: miRNA-target interactions (MTIs), protein-protein interactions, and gene-disease associations. Two contributing factors to functional miRNA-disease associations were quantitatively considered: the direct effects of miRNA that target disease-related genes, and indirect effects triggered by protein-protein interactions. Ninety-nine miRNAs were scanned for possible functional association with 2223 MeSH-defined human diseases. Each miRNA was experimentally validated to target ≥ 10 mRNA genes. Putative MDAs were identified when at least one MTI was confidently validated for a disease. Overall, 19648 putative MDAs were found, of which 10.0% was experimentally validated. Further results suggest that filtering for miRNAs that target a greater number of disease-related genes (n ≥ 8) can significantly enrich for true MDAs from the set of putative associations (enrichment rate = 60.7%, adjusted hypergeometric p = 2.41×10-91). Considering the indirect effects of miRNAs further elevated the enrichment rate to 72.6%. By using this method, a novel MDA between miR-24 and ovarian cancer was found. Compared with scramble miRNA overexpression of miR-24 was validated to remarkably induce ovarian cancer cells apoptosis. Our study provides novel insight into factors contributing to functional MDAs by integrating large quantities of previously generated biological data, and establishes a feasible method to identify plausible associations with high confidence.
authors: Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Harbin Medical University, Harbin, China.
authors: Dandan
authors: D
authors: Yuan
authors: School of Measurement and Control Technology & Communications Engineering, Harbin University of Science and Technology, Harbin, China.
authors: Xiaomeng
authors: X
authors: Cui
authors: Department of Pharmacy, the First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors: Yang
authors: Y
authors: Wang
authors: Department of Pharmacy, the First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors: Yilei
authors: Y
authors: Zhao
authors: Department of Obstetrics and Gynecology, Hongqi Hospital of Mudanjiang Medical University, Mudanjiang, China.
authors: Huiying
authors: H
authors: Li
authors: Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Harbin Medical University, Harbin, China.
authors: Suangjiu
authors: S
authors: Hu
authors: Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Harbin Medical University, Harbin, China.
authors: Xiaodan
authors: X
authors: Chu
authors: Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Harbin Medical University, Harbin, China.
authors: Yan
authors: Y
authors: Li
authors: Department of General Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, China.
authors: Qiang
authors: Q
authors: Li
authors: Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Harbin Medical University, Harbin, China.
authors: Qian
authors: Q
authors: Liu
authors: Institute of Clinical Pharmacology, the Second Affiliated Hospital of Harbin Medical University, Harbin, China.
authors: Wenliang
authors: W
authors: Zhu
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival; D057225:Data Mining; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D025941:Protein Interaction Mapping
chemical_list: C543845:MIRN24 microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins