MiR-1 targets PIK3CA and inhibits tumorigenic properties of A549 cells.
MicroRNAs are small endogenous RNAs that play important roles in the pathogenesis of human diseases, including malignancy. MicroRNA-1 (miR-1) is downregulated in non-small cell lung cancer (NSCLC); however, the underlying mechanisms by which it suppresses tumorigenesis in NSCLC are largely unknown. We investigated whether phosphoinositide-3-kinase catalytic subunit alpha (PIK3CA) was a novel target of miR-1 in the NSCLC cell line A549, and the mechanism of miR-1 inhibition of the tumorigenic properties of A549 cells is discussed. The influence of miR-1 on A549 cells was studied by transfection with miR-1 mimics or inhibitor. MiR-1 overexpression led to downregulation of PIK3CA protein, but not mRNA by western blot and quantitative real-time PCR, respectively. The dual-luciferase reporter assay confirmed that miR-1 targeted PIK3CA directly. PIK3CA downregulation by miR-1 mimics led to a significant reduction of phosphorylated Akt and survivin protein, the downstream targets of the PI3K/Akt pathway. Cell proliferation was studied using a cell counting kit. Migration and invasion were evaluated by Transwell and Matrigel assays, respectively. Cell cycle and apoptosis were detected by flow cytometry. The results were that miR-1 upregulation inhibited A549 cell proliferation, migration, and invasion. These findings indicate that miR-1 may play an important role in the pathogenesis of NSCLC by regulating PIK3CA through the PI3K/Akt pathway. Increasing miR-1 expression may provide a novel approach for NSCLC treatment.
Department of Oncology, First Affiliated Hospital of Nanjing Medical University, 300, Guangzhou Road, Nanjing, Jiangsu 210029, China.
Qian-Qian
QQ
Yu
Department of Oncology, First Affiliated Hospital of Nanjing Medical University, 300, Guangzhou Road, Nanjing, Jiangsu 210029, China.
Hao
H
Wu
Department of Oncology, First Affiliated Hospital of Nanjing Medical University, 300, Guangzhou Road, Nanjing, Jiangsu 210029, China.
Xiang
X
Huang
Department of Oncology, First Affiliated Hospital of Nanjing Medical University, 300, Guangzhou Road, Nanjing, Jiangsu 210029, China.
Hua
H
Shen
Department of Oncology, First Affiliated Hospital of Nanjing Medical University, 300, Guangzhou Road, Nanjing, Jiangsu 210029, China.
Yong-Qian
YQ
Shu
Department of Cardiothoracic Surgery, First Affiliated Hospital of Nanjing Medical University, 300, Guangzhou Road, Nanjing, Jiangsu 210029, China.
Bin
B
Zhang
Department of Oncology, First Affiliated Hospital of Nanjing Medical University, 300, Guangzhou Road, Nanjing, Jiangsu 210029, China.
Cheng-Cheng
CC
Xiang
Department of Oncology, First Affiliated Hospital of Nanjing Medical University, 300, Guangzhou Road, Nanjing, Jiangsu 210029, China.
Shao-Min
SM
Yu
Department of Oncology, First Affiliated Hospital of Nanjing Medical University, 300, Guangzhou Road, Nanjing, Jiangsu 210029, China. Electronic address: rhguo@njmu.edu.cn.
Ren-Hua
RH
Guo
Department of Cardiothoracic Surgery, First Affiliated Hospital of Nanjing Medical University, 300, Guangzhou Road, Nanjing, Jiangsu 210029, China. Electronic address: clbright0909@hotmail.com.
Liang
L
Chen
D017209:Apoptosis / Q000235:genetics*; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D058534:Class I Phosphatidylinositol 3-Kinases; D015536:Down-Regulation; D005434:Flow Cytometry; D017930:Genes, Reporter; D016147:Genes, Tumor Suppressor; D006801:Humans; D049410:Luciferases, Renilla / Q000235:genetics; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness; D009857:Oncogenes; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010957:Plasmids; D060888:Real-Time Polymerase Chain Reaction; D014162:Transfection
D058534:Class I Phosphatidylinositol 3-Kinases; D049410:Luciferases, Renilla; D035683:MicroRNAs; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; C544547:MIRN1 microRNA, human; C484760:PIK3CA protein, human
A549; Gene therapy; MicroRNA; Non-small cell lung cancer; PIK3CA; miR-1