title: Exosome-Carried microRNA-375 Inhibits Cell Progression and Dissemination via Bcl-2 Blocking in Colon Cancer.
abstract: OBJECTIVE
  Worldwide, colorectal cancer (CRC) is the third most common cancer in men and second in women. The aim of the current study was to identify whether the miR-375 is indeed down-regulated in metastatic CRC and if it could be considered as a potential minimally invasive prognostic biomarker for CRC.
  
  
  METHODS
  Exosomes were isolated and characterized from patients with liver metastasis from CCR. The characterization of exosome was performed using TEM/SEM. HCT116 cells were treated with miR-375 mimic, NSM and miR-375 inhibitor. Functional assays included cell counting assay for 14 days, Matrigel invasion assay, apoptosis assay by flow cytometry using Annexin V-FITC, RT-PCR and Western blotting.
  
  
  RESULTS
  Increased proliferation potential was proven for the cells transfected with miR-375 inhibitor, while the miR-375 mimic decreased the cell number. The cells transfected with the miR-375 inhibitor are aggressive and cross the membrane; 3.84% of the cells transfected with the miR-375 inhibitor entered apoptosis, while 6.45% of those transfected with the non-specific mimic were in programmed cell death, less than those transfected with the microRNA. RT-PCR for Bcl-2 expression showed that Bcl-2 is down-regulated for miR-375 inhibitor and up-regulated for the miR-375 mimic, a result confirmed by Western blotting.
  
  
  CONCLUSIONS
  The present study brings to the forefront new data that suggest miR-375 as a new player in controlling the pathways responsible for inhibiting the natural history of CRC tumor cells, via the Bcl-2 pathway.
authors.affiliation: Iuliu Hatieganu University of Medicine and Pharmacy;Dept. of Surgery, Octavian Fodor Regional Institute of Gastroenterology and Hepatology, Cluj-Napoca, Romania.
authors.forename: Florin
authors.initials: F
authors.lastname: Zaharie
authors.affiliation: Iuliu Hatieganu University of Medicine and Pharmacy;Dept. of Surgical and Gynecological Oncology, Ion Chiricuta Oncology Institute, Cluj-Napoca, Romania.
authors.forename: Mihai Stefan
authors.initials: MS
authors.lastname: Muresan
authors.affiliation: Dept of Pathology, Emergency County Hospital, Cluj-Napoca, Romania.
authors.forename: Bobe
authors.initials: B
authors.lastname: Petrushev
authors.affiliation: Animal Facility, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
authors.forename: Cristian
authors.initials: C
authors.lastname: Berce
authors.affiliation: Research Center for Functional Genomics and Translational Medicine Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
authors.forename: Grigore-Aristide
authors.initials: GA
authors.lastname: Gafencu
authors.affiliation: Research Center for Functional Genomics and Translational Medicine Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
authors.forename: Sonia
authors.initials: S
authors.lastname: Selicean
authors.affiliation: Research Center for Functional Genomics and Translational Medicine Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
authors.forename: Ancuta
authors.initials: A
authors.lastname: Jurj
authors.affiliation: Research Center for Functional Genomics and Translational Medicine Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
authors.forename: Roxana
authors.initials: R
authors.lastname: Cojocneanu-Petric
authors.affiliation: Iuliu Hatieganu University of Medicine and Pharmacy; Dept. of Surgical and Gynecological Oncology, Ion Chiricuta Oncology Institute, Cluj-Napoca, Romania.
authors.forename: Cosmin-Ioan
authors.initials: CI
authors.lastname: Lisencu
authors.affiliation: Research Center for Functional Genomics and Translational Medicine Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
authors.forename: Laura-Ancuta
authors.initials: LA
authors.lastname: Pop
authors.affiliation: Iuliu Hatieganu University of Medicine and Pharmacy;Research Center for Functional Genomics and Translational Medicine Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
authors.forename: Valentina
authors.initials: V
authors.lastname: Pileczki
authors.affiliation: Iuliu Hatieganu University of Medicine and Pharmacy;Dept. of Surgical and Gynecological Oncology, Ion Chiricuta Oncology Institute, Cluj-Napoca, Romania.
authors.forename: Dan
authors.initials: D
authors.lastname: Eniu
authors.affiliation: Iuliu Hatieganu University of Medicine and Pharmacy;Dept. of Surgical and Gynecological Oncology, Ion Chiricuta Oncology Institute, Cluj-Napoca, Romania.
authors.forename: Mihai-Andrei
authors.initials: MA
authors.lastname: Muresan
authors.affiliation: Iuliu Hatieganu University of Medicine and Pharmacy;Dept. of Gastroenterology Octavian Fodor Regional Institute of Gastroenterology and Hepatology, Cluj Napoca; Romania.
authors.forename: Roxana
authors.initials: R
authors.lastname: Zaharie
authors.affiliation: Research Center for Functional Genomics and Translational Medicine Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania;Dept. of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Ioana
authors.initials: I
authors.lastname: Berindan-Neagoe
authors.affiliation: Research Center for Functional Genomics and Translational Medicine Iuliu Hatieganu University of Medicine and Pharmacy;Dept. of Hematology, Ion Chiricuta Oncology Institute, Cluj Napoca, Romania. ciprian.tomuleasa@umfcluj.ro.
authors.forename: Ciprian
authors.initials: C
authors.lastname: Tomuleasa
authors.affiliation: Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
authors.forename: Alexandru
authors.initials: A
authors.lastname: Irimie
mesh_terms: D017209:Apoptosis; D002465:Cell Movement; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D055354:Exosomes / Q000378:metabolism* / Q000648:ultrastructure; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000556:secondary; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection
chemical_list: C000595707:BCL2 protein, human; C540933:MIRN375 microRNA, human; D035683:MicroRNAs; D019253:Proto-Oncogene Proteins c-bcl-2