MiR-454 promotes the progression of human non-small cell lung cancer and directly targets PTEN.
OBJECTIVE
MicroRNA-454 has been proven dysregulated in some human malignancies and correlated with tumor progression. However, its expression and function in non-small cell lung cancer (NSCLC) is still unclear. Thus, the aim of this study was to explore the effects of miR-454 in NSCLC tumorigenesis and development.


METHODS
Using quantitative RT-PCR, we detected miR-454 expression in NSCLC cell lines and primary tumor tissues. The association of miR-454 expression with clinicopathological factors and prognosis was also analyzed. Then, the effects of miR-454 on the biological behavior of NSCLC cells were investigated. At last, the potential regulatory function of miR-454 on PTEN expression was confirmed.


RESULTS
miR-454 was found to be up-regulated in NSCLC tissues and cell lines. High miR-454 expression was closely correlated with lymph node metastasis, advanced TNM stage, and shorter overall survival. Multivariate regression analysis corroborated that miR-454 overexpression was an independent unfavourable prognostic factor for patients with NSCLC. Down-regulation of miR-454 could significantly reduce NSCLC cell proliferation, enhance cell apoptosis, and impair cell invasion and migration in vitro, while up-regulation of miR-454 showed opposite effects. Further, PTEN was confirmed as a direct target of miR-454 by using Luciferase Reporter Assay.


CONCLUSIONS
These findings indicate that miR-454 may act as an oncogene in NSCLC and would serve as a potential therapy target for this disease.
Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, PR China.
Deng-Yan
DY
Zhu
Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, PR China.
Xiang-Nan
XN
Li
Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, PR China.
Yu
Y
Qi
Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, PR China.
Dong-Lei
DL
Liu
Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, PR China.
Yang
Y
Yang
Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, PR China.
Jia
J
Zhao
Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, PR China.
Chun-Yang
CY
Zhang
Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, PR China.
Kai
K
Wu
Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, PR China. Electronic address: manuzhaosong@163.com.
Song
S
Zhao
D001483:Base Sequence; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D015999:Multivariate Analysis; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis
C583712:MIRN454 microRNA, human; D035683:MicroRNAs; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
Apoptosis; MiR-454; Non-small cell lung cancer; PTEN; Prognosis; Proliferation