Affiliations: [a] Molecular Biology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran | [b] Genetic Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
Correspondence:
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Corresponding author: Mahmood Tavallaei, Genetic Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran. Tel.: +98 21 82482548; E-mail:[email protected]
Abstract: 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.
Keywords: Lung cancer, microRNAs, signaling pathway, systems biology
