A systems biology approach for miRNA-mRNA expression patterns analysis in non-small cell lung cancer.
Non-small cell lung cancers (NSCLCs) is a prevalent and heterogeneous subtype of lung cancer accounting for 85 percent of patients. MicroRNAs (miRNAs), a class of small endogenous non-coding RNAs, incorporate into regulation of gene expression post-transcriptionally. Therefore, deregulation of miRNAs' expression has provided further layers of complexity to the molecular etiology and pathogenesis of different diseases and malignancies. Although, until now considerable number of studies has been carried out to illuminate this complexity in NSCLC, they have remained less effective in their goal due to lack of a holistic and integrative systems biology approach which considers all natural elaborations of miRNAs' function. It is able to reliably nominate most affected signaling pathways and therapeutic target genes by deregulated miRNAs during a particular pathological condition. Herein, we utilized a holistic systems biology approach, based on appropriate re-analyses of microarray datasets followed by reliable data filtering, to analyze integrative and combinatorial deregulated miRNA-mRNA interaction network in NSCLC, aiming to ascertain miRNA-dysregulated signaling pathway and potential therapeutic miRNAs and mRNAs which represent a lion' share during various aspects of NSCLC's pathogenesis. Our systems biology approach introduced and nominated 1) important deregulated miRNAs in NSCLCs compared with normal tissue 2) significant and confident deregulated mRNAs which were anti-correlatively targeted by deregulated miRNA in NSCLCs and 3) dysregulated signaling pathways in association with deregulated miRNA-mRNAs interactions in NSCLCs. These results introduce possible mechanism of function of deregulated miRNAs and mRNAs in NSCLC that could be used as potential therapeutic targets.
Molecular Biology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.
Ali
A
Najafi
Genetic Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.
Mahmood
M
Tavallaei
Genetic Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.
Sayed Mostafa
SM
Hosseini
D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism; D019295:Computational Biology / Q000379:methods; D030541:Databases, Genetic; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D063990:Gene Ontology; D053263:Gene Regulatory Networks; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D025941:Protein Interaction Mapping / Q000379:methods; D060066:Protein Interaction Maps; D034622:RNA Interference; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics*; D015398:Signal Transduction; D049490:Systems Biology / Q000379:methods; D059467:Transcriptome
D035683:MicroRNAs; D012333:RNA, Messenger
Lung cancer; microRNAs; signaling pathway; systems biology