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.
Zhang
Ji-guang
JG
Thoracic Surgery Department, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, People's Republic of China.
Wang
Jian-jun
JJ
Zhao
Feng
F
Liu
Quan
Q
Jiang
Ke
K
Yang
Guang-hai
GH
D000368:Aged; D001665:Binding Sites / Q000235:genetics; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation / Q000235:genetics*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D051059:PTEN Phosphohydrolase / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism
D014408:Biomarkers, Tumor; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D025521:Tumor Suppressor Proteins; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human