MiR-1253 exerts tumor-suppressive effects in medulloblastoma via inhibition of CDK6 and CD276 (B7-H3).

Brain Pathology
Ranjana K KanchanSidharth Mahapatra

Abstract

Of the four primary subgroups of medulloblastoma, the most frequent cytogenetic abnormality, i17q, distinguishes Groups 3 and 4 which carry the highest mortality; haploinsufficiency of 17p13.3 is a marker for particularly poor prognosis. At the terminal end of this locus lies miR-1253, a brain-enriched microRNA that regulates bone morphogenic proteins during cerebellar development. We hypothesized miR-1253 confers novel tumor-suppressive properties in medulloblastoma. Using two different cohorts of medulloblastoma samples, we first studied the expression and methylation profiles of miR-1253. We then explored the anti-tumorigenic properties of miR-1253, in parallel with a biochemical analysis of apoptosis and proliferation, and isolated oncogenic targets using high-throughput screening. Deregulation of miR-1253 expression was noted, both in medulloblastoma clinical samples and cell lines, by epigenetic silencing via hypermethylation; specific de-methylation of miR-1253 not only resulted in rapid recovery of expression but also a sharp decline in tumor cell proliferation and target gene expression. Expression restoration also led to a reduction in tumor cell virulence, concomitant with activation of apoptotic pathways, cell cycle...Continue Reading

References

Nov 1, 1989·Genes, Chromosomes & Cancer·J A BiegelB S Emanuel
Jan 1, 1997·British Journal of Cancer·E Steichen-GersdorfF M Fink
Apr 3, 2001·Annual Review of Neuroscience·R Wechsler-Reya, M P Scott
Feb 20, 2004·Proceedings of the National Academy of Sciences of the United States of America·George Adrian CalinCarlo M Croce
Nov 3, 2004·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Ales CveklAles Cvekl
Nov 19, 2004·Nature·Joan Massagué
Jun 30, 2005·Cancer Metastasis Reviews·Marcin KortylewskiHua Yu
Nov 30, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Frank MendrzykPeter Lichter
Sep 23, 2006·Developmental Biology·Baohong ZhangTodd A Anderson
Feb 8, 2008·Cell Cycle·Melissa R Junttila, Jukka Westermarck
Feb 19, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Alessandra RossiAntonio Giordano
Mar 19, 2008·Genes & Development·Kimberly J BriggsD Neil Watkins
Jul 2, 2009·Nature Reviews. Drug Discovery·Silvia Lapenna, Antonio Giordano
May 25, 2010·Nature Reviews. Cancer·Bríd M RyanCurtis C Harris
Sep 9, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Paul A NorthcottMichael D Taylor
Jan 27, 2011·Acta Neuropathologica·David W EllisonRichard J Gilbertson
Jun 15, 2011·Oncotarget·Jonathan R Hart, Peter K Vogt
Nov 24, 2011·PloS One·Mariarosaria IncoronatoGerolama Condorelli
Jul 27, 2012·Nature·Paul A NorthcottMichael D Taylor
Jun 5, 2013·Translational Oncology·Hye Sook MinSung-Hye Park
Jun 27, 2013·Nature Reviews. Molecular Cell Biology·Stefan L Ameres, Phillip D Zamore
Mar 7, 2014·Cancer Research·Hideto KosoSumiko Watanabe
Aug 15, 2014·Nature Reviews. Molecular Cell Biology·Archana Shenoy, Robert H Blelloch
May 9, 2015·Science·Marta MeléRoderic Guigó
Dec 15, 2015·Cancer Discovery·Charles J SherrGeoffrey I Shapiro
Apr 5, 2016·Acta Neuropathologica·Vijay RamaswamyScott L Pomeroy
May 22, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Elodie PicardaXingxing Zang
Jun 14, 2017·Cancer Cell·Florence M G CavalliMichael D Taylor
Jun 24, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Michelle L Cook SangarJames M Olson
Feb 3, 2018·Methods in Molecular Biology·Jonathan Serrano, Matija Snuderl
Mar 15, 2018·Nature·David CapperStefan M Pfister
Apr 22, 2018·Biochemical and Biophysical Research Communications·Lipeng HuangWeiyang Yu

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Citations

Oct 15, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Filippos KontosSoldano Ferrone
Apr 4, 2021·International Journal of Molecular Sciences·Noora Karim AhangarBehzad Baradaran
Apr 11, 2021·Clinical and Experimental Medicine·Daye Yang, Dewei Zhang
Aug 28, 2021·Cancers·Pere Llinàs-AriasDiego M Marzese

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Methods Mentioned

BETA
genotyping
methylation profiling
transfection
Assay
PCR
xenograft
flow cytometry
acetylation
transfections

Clinical Trials Mentioned

NCT03709680

Software Mentioned

SOFTMAX PRO
R2
miRanda
GraphPad
Nanostring
Prism
RnBeads

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