title: MicroRNA-223 delivered by platelet-derived microvesicles promotes lung cancer cell invasion via targeting tumor suppressor EPB41L3.
abstract: BACKGROUND
  Patients with hematogenous metastatic lung cancer displayed significantly increased platelet count and aggregation compared to lung cancer patients without hematogenous metastasis. The mechanism underlying the correlation between the lung cancer hematogenous metastasis and platelet activation remains unknown.
  
  
  RESULTS
  In the present study, we explored the role of microRNA-223 (miR-223) derived from platelets in modulating lung cancer cell invasion. Our results demonstrated that platelets from NSCLC patients contain higher level of miR-223 than that from healthy subjects. The concentration of miR-223 in the platelet-secreted microvesicles (P-MVs) from NSCLC patients was also increased compared to that from healthy subjects. Incubation of human lung cancer A549 cells with P-MVs resulted in rapid delivery of miR-223 into A549 cells, in which platelet miR-223 targeted EPB41L3 and thus promoted A549 cell invasion. The effect of P-MVs on reducing EPB41L3 in A549 cells but promoting tumor cell invasion could be largely abolished by depletion of miR-223 via transfection with miR-223 antagomir. The role of EPB41L3 in inhibiting A549 cell invasion was further validated by directly downregulating EPB41L3 via transfecting cells with EPB41L3 siRNA or miR-223 mimic.
  
  
  CONCLUSIONS
  Our study demonstrates for the first time that platelet-secreted miR-223 via P-MVs can promote lung cancer cell invasion via targeting tumor suppressor EPB41L3.
authors.affiliation: From State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University School of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, Nanjing, Jiangsu, 210093, China. lianghongwei0418@163.com.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Liang
authors.affiliation: The Comprehensive Cancer Center of Drum Tower Hospital affiliated to Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, Jiangsu, 210008, China. yanxin8612@126.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Yan
authors.affiliation: From State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University School of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, Nanjing, Jiangsu, 210093, China. 46681998@qq.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Department of Respiratory Medicine, Nanjing Drum Tower Hospital Affiliated to Medical School of Nanjing University, 321 Zhongshan Road, Nanjing, 210008, Jiangsu Province, China. dolphin8012@yahoo.com.
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Wang
authors.affiliation: From State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University School of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, Nanjing, Jiangsu, 210093, China. claireaced@163.com.
authors.forename: Nan
authors.initials: N
authors.lastname: Wang
authors.affiliation: From State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University School of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, Nanjing, Jiangsu, 210093, China. bixuehan2005@163.com.
authors.forename: Limin
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Biology, Georgia State University, Atlanta, GA, 30303, USA. yliu@gsu.edu.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: From State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University School of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, Nanjing, Jiangsu, 210093, China. xichen@nju.edu.cn.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: From State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University School of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, Nanjing, Jiangsu, 210093, China. cyzhang@nju.edu.cn.
authors.forename: Chen-Yu
authors.initials: CY
authors.lastname: Zhang
authors.affiliation: From State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University School of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, Nanjing, Jiangsu, 210093, China. hongweigu@nju.edu.cn.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Gu
authors.affiliation: From State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University School of Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, Nanjing, Jiangsu, 210093, China. kzen@nju.edu.cn.|Department of Biology, Georgia State University, Atlanta, GA, 30303, USA. kzen@nju.edu.cn.
authors.forename: Ke
authors.initials: K
authors.lastname: Zen
mesh_terms: D000368:Aged; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D001792:Blood Platelets / Q000378:metabolism*; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D055252:Cell-Derived Microparticles / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics*; D008840:Microfilament Proteins / Q000737:chemistry / Q000235:genetics*; D008875:Middle Aged; D009367:Neoplasm Staging; D034622:RNA Interference; D012307:Risk Factors
chemical_list: D035683:MicroRNAs; D008840:Microfilament Proteins; C116887:EPB41L3 protein, human; C525067:MIR223, human