MicroRNA-21 (miR-21) represses tumor suppressor PTEN and promotes growth and invasion in non-small cell lung cancer (NSCLC)

• Published in: Clinica chimica acta Vol. 411; no. 11-12; pp. 846 - 852
• Main Authors: Zhang, Ji-guang, Wang, Jian-jun, Zhao, Feng, Liu, Quan, Jiang, Ke, Yang, Guang-hai
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 03.06.2010
• Subjects: Aged; Binding Sites - genetics; Biomarkers, Tumor - antagonists & inhibitors; Biomarkers, Tumor - biosynthesis; Biomarkers, Tumor - genetics; Carcinoma, Non-Small-Cell Lung - enzymology; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - pathology; Cell Line, Tumor; Cell Proliferation; Down-Regulation - genetics; Female; Humans; Invasion; Lung Neoplasms - enzymology; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Male; MicroRNA; MicroRNAs - biosynthesis; MicroRNAs - genetics; MicroRNAs - physiology; Middle Aged; miR-21; Neoplasm Invasiveness - genetics; Neoplasm Invasiveness - pathology; NSCLC; PTEN; PTEN Phosphohydrolase - antagonists & inhibitors; PTEN Phosphohydrolase - biosynthesis; PTEN Phosphohydrolase - metabolism; RNA Processing, Post-Transcriptional; Tumor Suppressor Proteins - antagonists & inhibitors; Tumor Suppressor Proteins - biosynthesis; Tumor Suppressor Proteins - metabolism; TNM; MicroRNA; NSCLC; miRNAs; FBS; qRT-PCR; PTEN; miR-21; Invasion
• ISSN: 0009-8981; 1873-3492
• DOI: 10.1016/j.cca.2010.02.074

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. 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. 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. 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.