Frequent abnormalities in 7p12 locus in different tumors like lung cancer candidate this region for novel regulatory elements. MiRNAs as novel regulatory elements encoded within the human genome are potentially oncomiRs or miR suppressors. Here, we have used bioinformatics tools to search for the novel miRNAs embedded within human chromosome 7p12. A bona fide stem loop (named mirZa precursor) had the features of producing a real miRNA (named miRZa) which was detected through RT-qPCR following the overexpression of its precursor. Then, endogenous miRZa was detected in human cell lines and tissues and sequenced. Consistent to the bioinformatics prediction, RT-qPCR as well as dual luciferase assay indicated that SMAD3 and IGF1R genes were targeted by miRZa. MiRZa-3p and miRZa-5p were downregulated in lung tumor tissue samples detected by RT-qPCR, and mirZa precursor overexpression in SW480 cells resulted in increased sub-G1 cell population. Overall, here we introduced a novel miRNA which is capable of targeting SMAD3 and IGF1R regulatory genes and increases the cell population in sub-G1 stage.

Selective pressures that trigger cancer formation and progression shape the mutational landscape of somatic mutations in cancer. Given the limits within which cells are regulated, a growing tumor has access to only a finite number of pathways that it can alter. As a result, tumors arising from different cells of origin often harbor identical genetic alterations. Recent expansive sequencing efforts have identified recurrent hotspot mutated residues in individual genes. Here, we introduce PhiDsc, a novel statistical method developed based on the hypothesis that, functional mutations in a recurrently aberrant gene family can guide the identification of mutated residues in the family's individual genes, with potential functional relevance. PhiDsc combines 3D structural alignment of related proteins with recurrence data for their mutated residues, to calculate the probability of randomness of the proposed mutation. The application of this approach to the RAS and RHO protein families returned known mutational hotspots as well as previously unrecognized mutated residues with potentially altering effect on protein stability and function. These mutations were located in, or in proximity to, active domains and were indicated as protein-altering according to six in silico predictors. PhiDsc is freely available at https://github.com/hobzy987/PhiDSC-DALI.