Mir-494-3p enhances aggressive phenotype of non-small cell lung cancer cells by regulating SET/I2PP2A

A high level of miR-494-3p expression has been associated with poor prognosis of non-small cell lung cancer (NSCLC) patients. However, its role in NSCLC development and progression remains elusive. Analyses of the Clinical Proteomic Tumor Analysis Consortium and the Cancer Genome Atlas databases showed overexpression of miR-494-3p in both lung adenocarcinoma and lung squamous cell carcinoma cases. Furthermore, bioinformatic analysis revealed that representative pathways associated with cancer metastasis were enriched with genes positively correlated with miR-494-3p expression levels, suggesting possible involvement of miR-494-3p in the aggressive properties of NSCLC. To identify potential targets of miR-494-3p, genes inversely correlated with miR-494-3p in the mRNA expression datasets of NSCLC cell lines obtained from the Cancer Dependency Map were examined in the present study. Integration of RNA sequencing analysis of NSCLC cells with miR-494-3p inhibition and a bioinformatic search of miRNA target prediction algorithms resulted in identification of SET/I2PP2A as a direct target of miR-494-3p. The findings indicate that suppression of SET/I2PP2A by miR-494-3p promotes NSCLC cell migration and invasion, but not viability, thus indicating miR-494-3p and its downstream molecules as potential therapeutic targets for aggressive NSCLC phenotypes.