title: MiR-93 Promotes Tumorigenesis and Metastasis of Non-Small Cell Lung Cancer Cells by Activating the PI3K/Akt Pathway via Inhibition ofLKB1/PTEN/CDKN1A.
abstract: BACKGROUND
  Non-small cell lung cancer (NSCLC) accounts for approximately 85% of clinical lung cancer cases. MicroRNA-93 (miR-93) is an oncomiR in many types of human cancer, exerting pivotal effects in the development and progression of malignancies, including NSCLC. However, the mechanism underlying miR-93 involvement in NSCLC is unknown. Our purpose was to reveal and explain this mechanism, with the goal of contributing to the development of new diagnostic biomarkers and individualized therapeutic tools.
  
  
  METHODS
  The expression of miR-93 was determined in NSCLC cell lines A549, H1975, and H1299. The cells were transfected with control plasmids (Mock group), miR-93 overexpression plasmids (miR-93 Up group), or miR-93 inhibitor plasmids (miR-93 Down group) to generate stable miR-93-overexpressing or -depleted cells. The effects of miR-93 on proliferation, migration, and invasion of these cells were determined. Thein vivoeffects of miR-93 on tumor metastasis were determined in an NSCLC xenograft mouse model. The molecular mechanisms underlying these effects were investigated via dual luciferase reporter assay and western blotting.
  
  
  RESULTS
  MiR-93 expression levels were significantly greater in the NSCLC cell lines than in normal lung epithelial cells. Cell proliferation, migration, and invasion were significantly stimulated by miR-93 upregulation (allP<0.05) and inhibited by miR-93 downregulation. Dual luciferase reporter assay demonstrated that miR-93 directly bound with the 3'-untranslated region of the tumor suppressor geneLKB1. Western blotting analysis indicated that miR-93 activated the PI3K/Akt pathway by inhibiting LKB1, PTEN, and p21. Increased expression of miR-93 induced significant hepatic metastasis of lung cancer in the xenograft mouse model.
  
  
  CONCLUSIONS
  Overexpression of miR-93 facilitates tumorigenesis and metastasis of NSCLC. These findings provide novel insight into the mechanism of miR-93 involvement in NSCLC, suggesting that miR-93 may serve as a potential therapeutic target.
authors.affiliation: Key Laboratory of Laboratory Medicine, Ministry of Education of China, Zhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Chunmei
authors.initials: C
authors.lastname: Li
authors.affiliation: Key Laboratory of Laboratory Medicine, Ministry of Education of China, Zhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Lyu
authors.affiliation: Key Laboratory of Laboratory Medicine, Ministry of Education of China, Zhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China;; Department of Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Qing H
authors.initials: QH
authors.lastname: Meng
keywords: LKB1; PI3K/Akt; metastasis.; miR-93; non-small cell lung cancer