MircoRNA-33a inhibits epithelial-to-mesenchymal transition and metastasis and could be a prognostic marker in non-small cell lung cancer.
Understanding the molecular mechanism by which epithelial mesenchymal transition (EMT)-mediated cancer metastasis and how microRNA (miRNA) regulates lung cancer progression via Twist1-activated EMT may provide potential therapeutic targets for cancer therapy. Here we found that miR-33a, an intronic miRNA located within the sterol regulatory element-binding protein 2 (SREBP-2) gene, is expressed at low levels in metastatic non-small cell lung cancer (NSCLC) cells and is inversely correlated with Twist1 expression. Conversely, miR-33a knockdown induces EMT and miR-33a overexpression blocks EMT by regulating of Twist1 expression in NSCLC cells. Bioinformatical prediction and luciferase reporter assay confirm that Twist1 is a direct target of miR-33a. Additionally, Twist1 knockdown blocks EMT-related metastasis and forced expression of miR-33a inhibits lung cancer metastasis in a xenograft animal model. Clinically, miR-33a is found to be at low levels in NSCLC patients and down-regulation of miR-33a predicts a poor prognosis. These findings suggest that miR-33a targets Twist1 and inhibits invasion and metastasis in NSCLC. Thus, miR-33a might be a potential prognostic marker and of therapeutic relevance for NSCLC metastasis intervention.
Institute of Biochemistry and Molecular Biology.|Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, ZJ 315211, China.
Lihua
L
Yang
Institute of Biochemistry and Molecular Biology.|Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, ZJ 315211, China.
Jie
J
Yang
Institute of Biochemistry and Molecular Biology.|Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, ZJ 315211, China.
Jingqiu
J
Li
Institute of Biochemistry and Molecular Biology.|Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, ZJ 315211, China.
Xingkai
X
Shen
Institute of Biochemistry and Molecular Biology.|Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, ZJ 315211, China.
Yanping
Y
Le
Department of Chest Surgery.
Chengwei
C
Zhou
Department of Oncology, The Affiliated Hospital of Ningbo University School of Medicine, Ningbo, ZJ 315020, China.
Shaomin
S
Wang
Clinical Laboratory, Ningbo No. 2 Hospital, Ningbo, ZJ 315010, China.
Shun
S
Zhang
State Key Laboratory of Oncology in South China.|Sun Yat-sen University Cancer Center, Guangzhou, GD 510060, China.
Dazhi
D
Xu
Institute of Biochemistry and Molecular Biology.|Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, ZJ 315211, China.
Zhaohui
Z
Gong
D000818:Animals; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D055785:Gene Knockdown Techniques; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D016513:Mice, SCID; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis; D009687:Nuclear Proteins / Q000378:metabolism; D011379:Prognosis; D051879:Twist-Related Protein 1 / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D014408:Biomarkers, Tumor; C550416:MIRN33a microRNA, human; D035683:MicroRNAs; D009687:Nuclear Proteins; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1