title: miR-let-7f-1 regulates SPARC mediated cisplatin resistance in medulloblastoma cells.
abstract: Our previous studies indicate that Secreted Protein Acidic and Rich in Cysteine (SPARC) expression suppressed medulloblastoma tumor growth in vitro and in vivo. Here we sought to determine the effect of SPARC expression in medulloblastoma cells to chemotherapeutic agents. In this study, we show that SPARC expression induces cisplatin resistance in medulloblastoma cells. We also demonstrate that the autophagy was involved in SPARC expression mediated resistance to cisplatin. Suppression of autophagy by either autophagy inhibitor, 3-methyladenosine (3MA) or Atg5 siRNA enhanced cisplatin sensitivity in SPARC expressed cells. Further, SPARC expression suppressed miR-let-7f-1 expression which resulted in disrupted repression of High Mobility Group Box 1 (HMGB1), a critical regulator of autophagy. We also show that HMGB1 is a direct target of miR-let-7f-1 and forced expression of HMGB1 cDNA enhanced cisplatin sensitivity in SPARC expressed cells. In summary, our results suggest that SPARC modulates cisplatin resistance by modulating the Let-7f-1 miRNA/HMGB1 axis in medulloblastoma cells.
authors.affiliation: From the Section of Hematology/Oncology, University of Illinois Cancer Center, College of Medicine at Chicago, Chicago, IL 60612, USA.
authors.forename: Padmavathi
authors.initials: P
authors.lastname: Pannuru
authors.affiliation: From the Section of Hematology/Oncology, University of Illinois Cancer Center, College of Medicine at Chicago, Chicago, IL 60612, USA.
authors.forename: Ranadheer
authors.initials: R
authors.lastname: Dontula
authors.affiliation: From the Section of Hematology/Oncology, University of Illinois Cancer Center, College of Medicine at Chicago, Chicago, IL 60612, USA.
authors.forename: Anwar A
authors.initials: AA
authors.lastname: Khan
authors.affiliation: Department of Neurosurgery, University of Illinois, College of Medicine at Chicago, Chicago, IL 60612, USA.
authors.forename: Englehard
authors.initials: E
authors.lastname: Herbert
authors.affiliation: From the Section of Hematology/Oncology, University of Illinois Cancer Center, College of Medicine at Chicago, Chicago, IL 60612, USA.
authors.forename: Howard
authors.initials: H
authors.lastname: Ozer
authors.affiliation: Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, IL 61605, USA.
authors.forename: Chandramu
authors.initials: C
authors.lastname: Chetty
authors.affiliation: From the Section of Hematology/Oncology, University of Illinois Cancer Center, College of Medicine at Chicago, Chicago, IL 60612, USA. Electronic address: slakka@uic.edu.
authors.forename: Sajani S
authors.initials: SS
authors.lastname: Lakka
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000633:toxicity; D001343:Autophagy / Q000187:drug effects; D000071187:Autophagy-Related Protein 5; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000633:toxicity; D019008:Drug Resistance, Neoplasm; D024243:HMGB1 Protein / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008527:Medulloblastoma / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015676:Osteonectin / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism
chemical_list: C502778:ATG5 protein, human; D000970:Antineoplastic Agents; D000071187:Autophagy-Related Protein 5; D024243:HMGB1 Protein; D035683:MicroRNAs; D008869:Microtubule-Associated Proteins; D015676:Osteonectin; D034741:RNA, Small Interfering; C577241:SPARC protein, human; C031080:3-methyladenosine; D000241:Adenosine; D002945:Cisplatin
keywords: Autophagy; HMGB1; Medulloblastoma; SPARC; miR-let-7f-1