Hsa-miR-1246 and hsa-miR-1290 are associated with stemness and invasiveness of non-small cell lung cancer.

Abstract

Cancer stem cells (CSCs) are considered to play a pivotal role in the process of invasion, metastasis and chemotherapy resistance. Diverse aberrantly expressed microRNAs (miRNAs) have been reported in lung cancer cells. However, there have been few reports about miRNAs that were associated with stemness and invasion of lung cancer. We investigated the role of miRNAs associated with characteristics of CSCs in non-small cell lung cancer (NSCLC). We cultured A549 cells (lung adenocarcinoma) and HCC1588 cells (lung squamous cell carcinoma) in serum free media condition. We isolated sphere-forming NSCLC cells and examined the microRNA expression by microarray and qRT-PCT. By inhibition of CSC-associated microRNAs, we identified the changes of stemness and invasiveness in NSCLC. We discovered 44 over-expressed, 42 down-regulated miRNAs in the sphere-forming cells compared with the parent cells of NSCLC. By in-silico database search, we selected miR-1246 and miR-1290 that were suspected to be associated with CSCs among aberrantly expressed miRNAs. Inhibition of miR-1246 and miR-1290 showed decreased stemness markers and epithelial-mesenchymal transition (EMT) markers in NSCLC. Anti-miR-1246 and anti-miR-1290 suppressed proliferation, sphere-formation, colony formation and invasion of NSCLC. CSCs-associated miR-1246, or miR-1290 may be important in the invasion or metastasis of NSCLC.