ABSTRACT
MicroRNAs (miRNAs) are single-stranded, 20-23 nucleotide-long RNA molecules that control gene expression in many cellular processes (Zhang 2009). These molecules bind to specifi c sequences in the 3’ untranslated region (3’UTR) of mRNAs to reduce their stability and translation effi ciency. miRNA genes can be expressed individually or within clusters, and can be found in introns of protein-coding genes as well as within repetitive regions and transposable elements (Huang et al. 2011). In oncogenesis, miRNAs have an important role in control of gene transcription, and based on their target, might be grouped in oncomiRNAs and miRNAs have been found to be deregulated in almost all human cancer, including lung cancer. miRNAs are involved in regulation of cellular processes linked to cancer as proliferation, differentiation, apoptosis, metastases and angiogenesis, however the exact molecular mechanisms leading to the malignant phenotype have not been unraveled yet (Garzon et al. 2006). The effects of miRNAs are mediated by modifi cation in their abundance in tumor cells; these changes may be due to aberrant expression owing to gene mutations and deletions, genomic instability and chromosomal fragile sites that generate abnormal DNA copy numbers. In addition, miRNA gene expression in cancer cells can be regulated by abnormal epigenetic modifi cations such as methylation of their promoter regions (Lujambio et al. 2008). MiRNAs frequently target hundreds of mRNAs, including those of genes that mediate processes in tumorigenesis, such as cell cycle regulation, cell proliferation, apoptosis, differentiation, metabolism, stress response, infl ammation and invasion (Hwang et al. 2006). The identifi cation of novel molecular markers in cancer is a high priority in order to reduce morbidity and mortality, and provide new strategies for targeted cancer therapy. In lung cancer, patient prognosis still remains poor. Consequently, new molecular therapies that target important pathways depending of EGFR and RAS have been developed. The genes of these molecules are known to be commonly mutated in lung cancer. Thus EGFR and KRAS are considered biomarkers in lung cancer. There are many studies that strongly support the potential of miRNAs as biomarkers. Some miRNAs are known to be intimately involved in regulation of KRAS
(Johnson et al. 2005), as well as in the initiation, progression and prognosis of NSCLC. More recently, miRNAs have been detected in peripheral blood of lung cancer patients (Fanini et al. 2011), which also makes them attractive candidates as biomarkers for noninvasive and early lung cancer diagnosis. The potential of restoring levels of aberrantly under-expressed miRNAs with miRNA mimics, or inactivating over-expressed miRNAs with miRNA inhibitors has been explored and could be the next generation of therapeutic strategies.
