Background: Non-small-cell lung cancer (NSCLC) is an aggressive neoplasm
with a poor survival and novel therapies are urgently needed. The study of deregulated micro-
RNAs (dereg-miRs) could constitute a strategy helping to detect specific genes playing a
relevant role in the disease. Thus, the oncoproteins encoded by these genes could be exploited
as novel therapeutic targets to be inhibited by small molecules, aptamers, or monoclonal
Methods: The present review is focused on candidate genes having convincing biological
evidences to be both bona fide targets for dereg-miRs and playing a role in NSCLC progression.
These genes were evaluated according to the molecular pathway they belong. Moreover,
in the attempt to provide an even broader list of candidate therapeutic targets for
NSCLC, the full list of genes was analyzed using the online tool Interactome DB.
Results: Among the identified targets, some of them belong to p53 or MAP kinase signaling
pathways, and others include caspases, MCL1, and BCL2L2 (playing a role in apoptosis), ZEB1, ZEB2, and
USP25 (epithelial-to-mesenchymal transition), EZH2, SOX9, and HOXA5 (differentiation), Paxillin, LIMK1 and
MTDH (cytoskeleton remodeling), and HDGF (angiogenesis). In addition, other targets, such as TIMP-2, PIM-1,
and components of the IGF-signaling pathways were suggested following the interactome analysis.
Conclusion: Studies on dereg-miRs helped to identify a set of genes whose encoded proteins could constitute
candidates for future therapeutic approaches.