MicroRNA-21 (miR-21) Represses Tumor Suppressor PTEN and Promotes Growth and Invasion in Non-small Cell Lung Cancer (NSCLC)

Background: MicroRNAs (miRNAs) are a class of small non-coding RNAs regulating gene expression that play roles in the pathogenesis of human diseases, including malignancy. miR-21, a commonly overexpressed miRNA in very diverse types of malignancies, may affect tumor progression through targeting tumor suppressor genes. We identified the role of miR-21 in non-small cell lung cancer (NSCLC) and to clarify the regulation of PTEN by miR-21 and determine mechanisms of this regulation.

Methods: Expression of miR-21 and PTEN in 20 paired NSCLC and adjacent non-tumor lung tissues was investigated by qRT-PCR and western blot, respectively. The effect of miR-21 on PTEN expression was assessed in NSCLC cell lines with miR-21 inhibitor to decrease miR-21 expression. Furthermore, the roles of miR-21 in cell growth and invasion were analyzed with miR-21 inhibitor-transfected cells.

Results: miR-21 was overexpressed in tumor tissues relative to adjacent non-tumor tissues. Notably, patients with advanced clinical TNM stage (n=16) or distal metastasis (n=5) demonstrated higher miR-21 expression than those without them (n=26, or n=37) (p<0.05, or p<0.001). Tumor tissues showed an inverse correlation between miR-21 and PTEN protein. miR-21 inhibitor transfection increased a luciferase-reporter activity containing the PTEN-3'-UTR construct and increased PTEN protein but not PTEN-mRNA levels in NSCLC cell lines. Finally, miR-21 inhibitor-transfected cells exhibited markedly reduced cell growth and invasive characteristics.

Conclusions: miR-21 post-transcriptionally down-regulates the expression of tumor suppressor PTEN and stimulates growth and invasion in NSCLC. It may be a potential therapeutic target for NSCLC.