title: HMGA1 silencing reduces stemness and temozolomide resistance in glioblastoma stem cells.
abstract: Glioblastoma multiforme (GBM) develops from a small subpopulation of stem-like cells, which are endowed with the ability to self-renew, proliferate and give rise to progeny of multiple neuroepithelial lineages. These cells are resistant to conventional chemo- and radiotherapy and are hence also responsible for tumor recurrence. HMGA1 overexpression has been shown to correlate with proliferation, invasion, and angiogenesis of GBMs and to affect self-renewal of cancer stem cells from colon cancer. The role of HMGA1 in GBM tumor stem cells is not completely understood.
  
  
  
  We have investigated the role of HMGA1 in brain tumor stem cell (BTSC) self-renewal, stemness and resistance to temozolomide by shRNA- mediated HMGA1 silencing.
  
  
  
  We first report that HMGA1 is overexpressed in a subset of BTSC lines from human GBMs. Then, we show that HMGA1 knockdown reduces self-renewal, sphere forming efficiency and stemness, and sensitizes BTSCs to temozolomide. Interestingly, HMGA1 silencing also leads to reduced tumor initiation ability in vivo.
  
  
  
  These results demonstrate a pivotal role of HMGA1 in cancer stem cell gliomagenesis and endorse HMGA1 as a suitable target for CSC-specific GBM therapy.
authors.affiliation: a Istituto di Endocrinologia ed Oncologia Sperimentale - CNR c/o Dipartimento di Medicina Molecolare e Biotecnologie Mediche , Università degli Studi di Napoli 'Federico II,' Naples , Italy.
authors.forename: Marianna
authors.initials: M
authors.lastname: Colamaio
authors.affiliation: a Istituto di Endocrinologia ed Oncologia Sperimentale - CNR c/o Dipartimento di Medicina Molecolare e Biotecnologie Mediche , Università degli Studi di Napoli 'Federico II,' Naples , Italy.|b Molecular Pathology Unit, Institute of Pathology , University Hospital Basel , Basel , Switzerland.
authors.forename: Nadia
authors.initials: N
authors.lastname: Tosti
authors.affiliation: a Istituto di Endocrinologia ed Oncologia Sperimentale - CNR c/o Dipartimento di Medicina Molecolare e Biotecnologie Mediche , Università degli Studi di Napoli 'Federico II,' Naples , Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Puca
authors.affiliation: a Istituto di Endocrinologia ed Oncologia Sperimentale - CNR c/o Dipartimento di Medicina Molecolare e Biotecnologie Mediche , Università degli Studi di Napoli 'Federico II,' Naples , Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Mari
authors.affiliation: a Istituto di Endocrinologia ed Oncologia Sperimentale - CNR c/o Dipartimento di Medicina Molecolare e Biotecnologie Mediche , Università degli Studi di Napoli 'Federico II,' Naples , Italy.
authors.forename: Rosaria
authors.initials: R
authors.lastname: Gattordo
authors.affiliation: a Istituto di Endocrinologia ed Oncologia Sperimentale - CNR c/o Dipartimento di Medicina Molecolare e Biotecnologie Mediche , Università degli Studi di Napoli 'Federico II,' Naples , Italy.
authors.forename: Yalçın
authors.initials: Y
authors.lastname: Kuzay
authors.affiliation: a Istituto di Endocrinologia ed Oncologia Sperimentale - CNR c/o Dipartimento di Medicina Molecolare e Biotecnologie Mediche , Università degli Studi di Napoli 'Federico II,' Naples , Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Federico
authors.affiliation: c Dipartimento di Medicina Molecolare e Biotecnologie Mediche , Università degli Studi di Napoli 'Federico II,' Naples , Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Pepe
authors.affiliation: d CEINGE-Biotecnologie Avanzate , Naples , Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Sarnataro
authors.affiliation: a Istituto di Endocrinologia ed Oncologia Sperimentale - CNR c/o Dipartimento di Medicina Molecolare e Biotecnologie Mediche , Università degli Studi di Napoli 'Federico II,' Naples , Italy.
authors.forename: Elvira
authors.initials: E
authors.lastname: Ragozzino
authors.affiliation: d CEINGE-Biotecnologie Avanzate , Naples , Italy.
authors.forename: Maddalena
authors.initials: M
authors.lastname: Raia
authors.affiliation: e Department of Surgery , Kyushu University Beppu Hospital , Beppu , Japan.
authors.forename: Hidenari
authors.initials: H
authors.lastname: Hirata
authors.affiliation: d CEINGE-Biotecnologie Avanzate , Naples , Italy.
authors.forename: Marica
authors.initials: M
authors.lastname: Gemei
authors.affiliation: e Department of Surgery , Kyushu University Beppu Hospital , Beppu , Japan.
authors.forename: Koshi
authors.initials: K
authors.lastname: Mimori
authors.affiliation: d CEINGE-Biotecnologie Avanzate , Naples , Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Del Vecchio
authors.affiliation: a Istituto di Endocrinologia ed Oncologia Sperimentale - CNR c/o Dipartimento di Medicina Molecolare e Biotecnologie Mediche , Università degli Studi di Napoli 'Federico II,' Naples , Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Battista
authors.affiliation: a Istituto di Endocrinologia ed Oncologia Sperimentale - CNR c/o Dipartimento di Medicina Molecolare e Biotecnologie Mediche , Università degli Studi di Napoli 'Federico II,' Naples , Italy.|f Programa de Carcinogênese Molecular , Instituto Nacional de Câncer - INCA , Rio de Janeiro , Brazil.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Fusco
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D005909:Glioblastoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D025741:HMGA1a Protein / Q000235:genetics*; D006801:Humans; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D000077204:Temozolomide
chemical_list: D018906:Antineoplastic Agents, Alkylating; D034741:RNA, Small Interfering; D025741:HMGA1a Protein; D003606:Dacarbazine; D000077204:Temozolomide
keywords: HMGA1; MGMT; cancer stem cells; glioblastoma; temozolomide