title: Restitution of Tumor Suppressor MicroRNA-145 Using Magnetic Nanoformulation for Pancreatic Cancer Therapy.
abstract: The functional significance of lost microRNAs has been reported in several human malignancies, including pancreatic cancer (PC). Our prior work has identified microRNA-145 (miR-145) as a tumor suppressor microRNA (miRNA) in pancreatic cancer. The restoration of miR-145 downregulates a number of oncogenes including mucin MUC13, a transmembrane glycoprotein that is aberrantly expressed in pancreatic cancer, thus efficiently inhibiting tumor growth in mice. However, lack of an effective tumor-specific delivery system remains an unmet clinical challenge for successful translation of microRNAs.
  
  
  
  We developed a miRNA-145-based magnetic nanoparticle formulation (miR-145-MNPF) and assessed its anti-cancer efficacy. Physico-chemical characterization (dynamic light scattering (DLS), transmission electron microscopy (TEM) and miR-binding efficiency), cellular internalization (Prussian blue and confocal microscopy), miR-145 restitution potential (quantitative reverse-transcription PCR (qRT-PCR), and anti-cancer efficacy (proliferation, colony formation, cell migration, cell invasion assays) of this formulation were performed using clinically relevant pancreatic cancer cell lines (HPAF-II, AsPC-1).
  
  
  
  miR-145-MNPF exhibited optimal particle size and zeta potential which effectively internalized and restituted miR-145 in pancreatic cancer cells. miR-145 re-expression resulted in downregulation of MUC13, HER2, pAKT, and inhibition of cell proliferation, clonogenicity, migration, and invasion of pancreatic cancer cells.
  
  
  
  miR-145-MNPF is an efficient system for miR-145 delivery and restitution in pancreas cancer that may offer a potential therapeutic treatment for PC either alone or in conjunction with conventional treatment.
authors: Department of Pharmaceutical Sciences and Center for Cancer Research, University of Tennessee Health Science Center, 19 South Manassas, Cancer Research Building, Memphis, TN, USA.
authors: Saini
authors: S
authors: Setua
authors: Department of Pharmaceutical Sciences and Center for Cancer Research, University of Tennessee Health Science Center, 19 South Manassas, Cancer Research Building, Memphis, TN, USA.
authors: Sheema
authors: S
authors: Khan
authors: Department of Pharmaceutical Sciences and Center for Cancer Research, University of Tennessee Health Science Center, 19 South Manassas, Cancer Research Building, Memphis, TN, USA.
authors: Murali M
authors: MM
authors: Yallapu
authors: Department of Surgery, University of Tennessee Health Science Center, Memphis, TN, USA.
authors: Stephen W
authors: SW
authors: Behrman
authors: Department of Pharmaceutical Sciences and Center for Cancer Research, University of Tennessee Health Science Center, 19 South Manassas, Cancer Research Building, Memphis, TN, USA.
authors: Mohammed
authors: M
authors: Sikander
authors: Department of Computer Science, University of Kashmir, Srinagar, Jammu and Kashmir, India.
authors: Shabia Shabir
authors: SS
authors: Khan
authors: Department of Pharmaceutical Sciences and Center for Cancer Research, University of Tennessee Health Science Center, 19 South Manassas, Cancer Research Building, Memphis, TN, USA.
authors: Meena
authors: M
authors: Jaggi
authors: Department of Pharmaceutical Sciences and Center for Cancer Research, University of Tennessee Health Science Center, 19 South Manassas, Cancer Research Building, Memphis, TN, USA. schauha1@uthsc.edu.
authors: Subhash C
authors: SC
authors: Chauhan
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D058185:Magnetite Nanoparticles / Q000627:therapeutic use*; D035683:MicroRNAs / Q000235:genetics*; D009077:Mucins / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: C429552:MUC13 protein, human; D058185:Magnetite Nanoparticles; D035683:MicroRNAs; D009077:Mucins
keywords: Magnetic nanoparticle; Nanotherapies; Pancreatic cancer; Therapeutics; miR-145