miR-23b/SP1/c-myc forms a feed-forward loop supporting multiple myeloma cell growth

Blood Cancer Journal
Mariateresa FulcinitiNikhil C Munshi

Abstract

Deregulated microRNA (miR)/transcription factor (TF)-based networks represent a hallmark of cancer. We report here a novel c-Myc/miR-23b/Sp1 feed-forward loop with a critical role in multiple myeloma (MM) and Waldenstrom's macroglobulinemia (WM) cell growth and survival. We have found miR-23b to be downregulated in MM and WM cells especially in the presence of components of the tumor bone marrow milieu. Promoter methylation is one mechanism of miR-23b suppression in myeloma. In gain-of-function studies using miR-23b mimics-transfected or in miR-23b-stably expressing MM and WM cell lines, we observed a significant decrease in cell proliferation and survival, along with induction of caspase-3/7 activity over time, thus supporting a tumor suppressor role for miR-23b. At the molecular level, miR-23b targeted Sp1 3'UTR and significantly reduced Sp1-driven nuclear factor-κB activity. Finally, c-Myc, an important oncogenic transcription factor known to stimulate MM cell proliferation, transcriptionally repressed miR-23b. Thus MYC-dependent miR-23b repression in myeloma cells may promote activation of oncogenic Sp1-mediated signaling, representing the first feed-forward loop with critical growth and survival role in myeloma.

References

Nov 26, 1999·Gene·G Suske
Jun 26, 2001·Journal of Cellular Physiology·A R BlackJ Azizkhan-Clifford
Oct 8, 2003·Proceedings of the National Academy of Sciences of the United States of America·S Mangan, U Alon
Dec 11, 2007·Nature Genetics·Tsung-Cheng ChangJoshua T Mendell
Mar 29, 2008·Science·Oliver Hobert
Oct 17, 2008·Genes & Development·Martin Eilers, Robert N Eisenman
Mar 11, 2009·Nature Reviews. Genetics·Juan M VaquerizasNicholas M Luscombe
Aug 23, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Mariateresa FulcinitiNikhil C Munshi
Sep 18, 2012·Neuroscience Letters·Jiong GengZhengxiang Yang
Oct 27, 2012·Oncotarget·Nicola AmodioPierfrancesco Tassone
Mar 12, 2013·Clinical Lymphoma, Myeloma & Leukemia·Antonio SaccoAldo M Roccaro
Apr 13, 2013·Nucleic Acids Research·Loredana PellegrinoLeandro Castellano
Apr 25, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Marta LionettiAntonino Neri
May 23, 2013·Expert Opinion on Biological Therapy·Nicola AmodioPierfrancesco Tassone
Sep 21, 2013·Current Opinion in Oncology·Jennifer E YehDavid A Frank
Apr 1, 2014·Molecular and Cellular Endocrinology·Vincenza LeoneAlfredo Fusco
Apr 24, 2014·Cancer Letters·Massimo DonadelliMarta Palmieri
May 15, 2015·Oncotarget·Nicola AmodioPierfrancesco Tassone

❮ Previous
Next ❯

Citations

Nov 29, 2016·Expert Opinion on Therapeutic Targets·Nicola AmodioDina Bellizzi
Mar 2, 2017·International Journal of Molecular Sciences·Rocío Retamales-OrtegaCarmen Romero
Jul 13, 2018·European Journal of Haematology·Hanne E H MøllerMichael B Møller
Aug 28, 2018·Expert Review of Hematology·Daniele CaraccioloPierfrancesco Tassone
Jan 19, 2019·Non-coding RNA·Irena Misiewicz-KrzeminskaNorma C Gutiérrez
May 6, 2019·Non-coding RNA·Cinzia FedericoAldo M Roccaro
Jul 4, 2019·International Journal of Molecular Sciences·Michela ColomboRaffaella Chiaramonte
Sep 14, 2019·International Journal of Molecular Sciences·Yang-Hsiang Lin
Jun 2, 2016·American Society of Clinical Oncology Educational Book·Raphael Szalat, Nikhil C Munshi
Feb 6, 2020·Cancers·Eugenio MorelliNicola Amodio
Jan 2, 2018·Oncotarget·Maria Angelica StamatoNicola Amodio
May 12, 2020·Cancer Biomarkers : Section a of Disease Markers·Jakob Benjamin Wilhelm WeissRoland Kappler
Aug 20, 2020·Technology in Cancer Research & Treatment·Zhaoyu LiuYongheng Yang
May 4, 2018·Frontiers in Immunology·Theresa KordaßStefan B Eichmüller
Jun 20, 2020·Pharmacological Reviews·Tae Jin LeeHolger K Eltzschig
May 10, 2018·Journal of Hematology & Oncology·Nicola AmodioPierfrancesco Tassone
Apr 30, 2020·Signal Transduction and Targeted Therapy·Chao NiJian Huang
Oct 21, 2020·Cancers·Cinzia CaprioAldo M Roccaro
Jan 27, 2021·Cancers·Timon A BloedjesJeroen E J Guikema
Apr 4, 2021·Biomedicines·Pinelopi I ArtemakiChristos K Kontos

❮ Previous
Next ❯

Methods Mentioned

BETA
density gradient sedimentation
transfection
PCR
Assay
in vitro transcription
chips

Software Mentioned

EpiDesigner
Ensemble Genome Browser
SureFIND
EpiTYPER
Graphpad
SPSS
Sequenom

Related Concepts