%0 Generic %A Colamaio, Marianna %A Tosti, Nadia %A Puca, Francesca %A Mari, Alessia %A Gattordo, Rosaria %A Kuzay, Yalçın %A Federico, Antonella %A Pepe, Anna %A Sarnataro, Daniela %A Ragozzino, Elvira %A Raia, Maddalena %A Hirata, Hidenari %A Gemei, Marica %A Mimori, Koshi %A del Vecchio, Luigi %A Battista, Sabrina %A Fusco, Alfredo %D 2016 %T HMGA1 silencing reduces stemness and temozolomide resistance in glioblastoma stem cells %U https://tandf.figshare.com/articles/dataset/HMGA1_silencing_reduces_stemness_and_temozolomide_resistance_in_glioblastoma_stem_cells/3812274 %R 10.6084/m9.figshare.3812274.v1 %2 https://tandf.figshare.com/ndownloader/files/5936589 %2 https://tandf.figshare.com/ndownloader/files/5936595 %2 https://tandf.figshare.com/ndownloader/files/5936598 %K HMGA1 %K cancer stem cells %K glioblastoma %K MGMT %K temozolomide %X

Objective: 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.

Research design and methods: 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.

Results: 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.

Conclusions: 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.

%I Taylor & Francis