Therapeutic Use of MicroRNAs in Lung Cancer

Abstract

Lung cancer is a leading cause of cancer deaths worldwide. Although the molecular pathways of lung cancer have been partly known, the high mortality rate is not markedly changed. MicroRNAs (miRNAs) are small noncoding RNAs that actively modulate cell physiological processes as apoptosis, cell-cycle control, cell proliferation, DNA repair, and metabolism. Several studies demonstrated that miRNAs are involved in the pathogenesis of lung diseases including lung cancer and they negatively regulate gene and protein expression by acting as oncogenes or tumor suppressors. In this review we summarize the current knowledge on the role of miRNAs and their target genes in lung tumorigenesis and evaluate their potential use as therapeutic agents in lung cancer. In particular, we describe methodological approaches such as inhibition of oncogenic miRNAs or replacement of tumor suppressor miRNAs, both in in vitro and in vivo assays. Furthermore we discuss new strategies to achieve in vivo tissue specific delivery, potential off-target effects, and safety of miRNAs systemic delivery.

miRNAs as Biomarkers and Therapeutic Targets in Non-Small Cell Lung Cancer: Current Perspectives

“…Recent studies have focused on aberrant expression of the let-7 and miR-34 families in lung tumour tissues when compared to the normal lung tissue, which can indicate the involvement of those miRNAs in lung carcinogenesis [169].…”

MiR‐199a‐5p suppresses tumorigenesis by targeting clathrin heavy chain in hepatocellular carcinoma

“…Deregulation of miRNAs has been observed in a wide range of human diseases, including HCC or other cancers . Our previous study identified several deregulated miRNAs in HCC tumor tissues (data not shown), of which miR‐199a‐5p was the most significance (Fold change: 0.0023, p <0.001).…”

“…9 Deregulation of miRNAs has been observed in a wide range of human diseases, including HCC or other cancers. [10][11][12][13][14][15] Our previous study identified several deregulated miRNAs in HCC tumor tissues (data not shown), of which miR-199a-5p was the most significance (Fold change: 0.0023, p<0.001). Although down-regulation of miR-199a-5p has been reported by others, the roles of miR-199a-5p and its novel targets are still worthy to be studied.…”

Nanocomplexes for gene therapy of respiratory diseases: Targeting and overcoming the mucus barrier

“…Antagomirs (synthetic analogues of miRNA) can induce a specific and long-lasting silencing of miRNAs and thereby can control gene expression [142]. Delivery of miRNAs as synthetic miRNA mimics or antagomirs has emerged as a promising approach to treat lung cancer, and this topic has been recently reviewed [143]. Among the different non-viral nanosized systems used to deliver miRNAs to the lung were solid lipid nanoparticles (SLNs) containing dimethyldioctadecylammonium bromide (DDAB) [144], liposomal formulations containing either DOTMA [145] or NOV340/miR-200c (SMARTICLES; a proprietary liposomal formulation containing amphoteric lipids that are cationic at low pH and neutral or anionic at neutral and higher pH) [146].…”