MiR-584-5p potentiates vincristine and radiation response by inducing spindle defects and DNA damage in medulloblastoma
Year: 2018
Type: article
Abstract: Despite improvements in overall survival, only a modest percentage of patients survives high-risk medulloblastoma. The devastating side effects of radiation and chemotherapy substantially reduce quality of life for surviving patients. Here, using genomic screens, we identified miR-584-5p as a potent therapeutic adjuvant that potentiates medulloblastoma to radiation and vincristine. MiR-584-5p inhibited medulloblastoma growth and prolonged survival of mice in pre-clinical tumor models. MiR-584-5p overexpression caused cell cycle arrest, DNA damage, and spindle defects in medulloblastoma cells. MiR-584-5p mediated its tumor suppressor and therapy-sensitizing effects by targeting HDAC1 and eIF4E3. MiR-584-5p overexpression or HDAC1/eIF4E3 silencing inhibited medulloblastoma stem cell self-renewal without affecting neural stem cell growth. In medulloblastoma patients, reduced expression of miR-584-5p correlated with increased levels of HDAC1/eIF4E3. These findings identify a previously undefined role for miR-584-5p/HDAC1/eIF4E3 in regulating DNA repair, microtubule dynamics, and stemness in medulloblastoma and set the stage for a new way to treat medulloblastoma using miR-584-5p.
Source: Nature Communications
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Awards: G1143455775, Mays Cancer Center at UT Health SA, G1351874825, G2364411900, G2396357632, G3582224020, G3934442055, G4352764696, Cancer Research Training Grant, G5550184716, G5827286289, Cancer Biology Training Program, G6633334197, G6679327881, UTHSCSA Cancer Research Training Program, G7297754420, miRNAs:Safe and effective therapeutic adjuvants for treating drug resistant TNBC, G9000285072, G9000293187, G9000324485
OpenAlex ID: W2898511841