title: MicroRNA-130b promotes lung cancer progression via PPARγ/VEGF-A/BCL-2-mediated suppression of apoptosis.
abstract: The prognosis of non-small-cell lung cancer (NSCLC) is poor yet mechanistic understanding and therapeutic options remain limited. We investigated the biological and clinical significance of microRNA-130b and its relationship with apoptosis in NSCLC.
  
  
  
  The level of microRNA-130b in relationship with the expression of PPARγ, VEGF-A, BCL-2 and apoptosis were analyzed in 91 lung cancer patient samples using immunohistochemistry and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay on tissue microarrays. Gain and loss-of-function studies were performed to investigate the effects of microRNA-130b, peroxisome proliferator-activated receptor γ (PPARγ) or vascular endothelial growth factor-A (VEGF-A) on biological functions of lung cancer cells using in vitro and in vivo approaches.
  
  
  
  MicroRNA-130b up-regulation conferred unfavorable prognosis of lung cancer patients. Notably, microRNA-130b targeted PPARγ and inhibiting microRNA-130b markedly repressed proliferation, invasion and metastasis of lung cancer cells, leading to increased apoptosis. MicroRNA-130b-dependent biologic effects were due to suppression of PPARγ that in turn activated BCL-2, the key mediator of anti-apoptosis. Administration of microRNA-130b mimic to mouse xenografts promoted tumor growth. In vitro and in vivo, miR-130b enrichment associated with down-regulation of PPARγ, up-regulation of VEGF-A and BCL-2, and decreased apoptosis.
  
  
  
  The present study demonstrates that microRNA-130b promotes lung cancer progression via PPARγ/VEGF-A/BCL-2-mediated suppression of apoptosis. Targeting microRNA-130b might have remarkable therapeutic potential for lung cancer therapy.
authors.affiliation: State Key Laboratory for Organ Failure Research, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Tian
authors.affiliation: State Key Laboratory for Organ Failure Research, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Hu
authors.affiliation: State Key Laboratory for Organ Failure Research, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China.|Department of Emergency, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Geng
authors.affiliation: Health Management Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Dai
authors.affiliation: State Key Laboratory for Organ Failure Research, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China. xiaoyanb@126.com.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Bai
mesh_terms: D000072283:A549 Cells; D000818:Animals; D017209:Apoptosis; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D018450:Disease Progression; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009368:Neoplasm Transplantation; D047495:PPAR gamma / Q000378:metabolism*; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D046888:Tissue Array Analysis; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: C554019:MIRN130 microRNA, human; D035683:MicroRNAs; D047495:PPAR gamma; D019253:Proto-Oncogene Proteins c-bcl-2; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A
keywords: Apoptosis; BCL-2; MicroRNA-130b; NSCLC; PPARγ