Role of miR-497 in VEGF-A-mediated cancer cell growth and invasion in non-small cell lung cancer.
The malignancy of non-small cell lung cancer (NSCLC) is largely due to its invasion. Hence, prevention of the cancer cell invasion, which is essentially regulated by vascular endothelial growth factor A (VEGF-A), is substantially critical for a successful treatment for NSCLC. Here, we showed that compared to other cancers, NSCLC had a significant higher ratio of VEGF-A protein vs mRNA, and significantly lower levels of miR-497, suggesting presence of a post-transcriptional control of VEGF-A in NSCLC different from other cancers. Compared with paired normal lung tissue, NSCLC expressed lower levels of miR-497 and higher levels of VEGF-A. Moreover, the levels of miR-497 and VEGF-A were inversely correlated in NSCLC specimen. Bioinformatics analyses showed that miR-497 bound to 3'-UTR of VEGF-A mRNA in NSCLC lines to inhibit its translation. Overexpression of miR-497 in NSCLC lines decreased VEGF-A protein, while depletion of miR-497 in NSCLC lines increased VEGF-A protein. However, modification of miR-497 levels in NSCLC lines did not alter VEGF-A mRNA levels. Overexpression of miR-497 in NSCLC lines inhibited cell growth and invasion, while depletion of miR-497 in NSCLC lines increased cell growth and invasion. Together, our data demonstrate a previously unappreciated role for miR-497 in suppression of VEGF-A-mediated NSCLC cancer cell growth and invasion.
Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China.
Aiqin
A
Gu
International Medical Care Center, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai 200080, China.
Jianhong
J
Lu
Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China.
Weimin
W
Wang
Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China.
Chunlei
C
Shi
Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China. Electronic address: hanbao_hui@163.com.
Baohui
B
Han
State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China. Electronic address: myao@shsci.org.
Ming
M
Yao
D001483:Base Sequence; D001665:Binding Sites; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D019295:Computational Biology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D009928:Organ Specificity; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
C559640:MIRN497 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A
Bioinformatics analyses; MiR-497; MiRNAs; Non-small cell lung cancer (NSCLC); Vascular endothelial growth factor A (VEGF-A)