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

High expression of miR-494-3p have been associated with poor prognosis in non-small cell lung cancer (NSCLC). However, the role of miR-494-3p in the development and progression of NSCLC remains elusive. In this study, we found that miR-494-3p was overexpressed in both lung adenocarcinoma and lung squamous cell carcinoma in the Clinical Proteomic Tumor Analysis Consortium and Cancer Genome Atlas databases. A bioinformatic analysis revealed that representative pathways associated with cancer metastasis were enriched in the genes positively correlated with miR-494-3p expression levels, suggesting the potential involvement of miR-494-3p in aggressive properties of NSCLC. To identify potential targets of miR-494-3p, we explored genes inversely correlated with miR-494-3p in the mRNA expression datasets of NSCLC cell lines obtained from the Cancer Dependency Map. 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. We found that suppression of SET/I2PP2A by miR-494-3p promoted cell migration and invasion, but not cell viability, in NSCLC cells, indicative of miR-494-3p and its downstream molecules as potential therapeutic targets in NSCLC with aggressive phenotypes. Overall design: RNA-seq profilling of NCI-H2030 cells treated with miR-494-3p AS or SC.