Fbw7 Inhibits the Progression of Activated B-Cell Like Diffuse Large B-Cell Lymphoma by Targeting the Positive Feedback Loop of the LDHA/lactate/miR-223 Axis.
Fbw7
LDHA
Lactate
activated B-cell
diffuse large B-cell lymphoma
miR-223
ubiquitination
Journal
Frontiers in oncology
ISSN: 2234-943X
Titre abrégé: Front Oncol
Pays: Switzerland
ID NLM: 101568867
Informations de publication
Date de publication:
2022
2022
Historique:
received:
23
12
2021
accepted:
17
02
2022
entrez:
1
4
2022
pubmed:
2
4
2022
medline:
2
4
2022
Statut:
epublish
Résumé
F-box and WD repeat domain-containing 7 (Fbw7) is well known as a tumor suppressor and ubiquitin ligase which targets a variety of oncogenic proteins for proteolysis. We previously reported that Fbw7 promotes apoptosis in diffuse large B-cell lymphoma (DLBCL) through Fbw7-mediated ubiquitination of Stat3. This study aimed to identify the mechanism of Fbw7-mediated aerobic glycolysis reprogramming in DLBCL. Expression levels of Fbw7 and Lactate Dehydrogenase A (LDHA) in human DLBCL samples were evaluated by immunohistochemistry. Crosstalk between Fbw7 and LDHA signaling was analyzed by co-immunoprecipitation, ubiquitination assay, western blotting and mRNA quanlitative analyses. Fbw7 could interact with LDHA to trigger its ubiquitination and degradation. Inversely, lactate negatively regulated Fbw7 We demonstrated that the ubiquitin-ligase Fbw7 played a key role in LDHA-related aerobic glycolysis reprogramming in DLBCL. Our study uncovers a negative functional loop consisting of a Fbw7-mediated LDHA/lactate/miR-223 axis, which may support the future ABC-DLBCL therapy by targeting LDHA-related inhibition.
Sections du résumé
Background
UNASSIGNED
F-box and WD repeat domain-containing 7 (Fbw7) is well known as a tumor suppressor and ubiquitin ligase which targets a variety of oncogenic proteins for proteolysis. We previously reported that Fbw7 promotes apoptosis in diffuse large B-cell lymphoma (DLBCL) through Fbw7-mediated ubiquitination of Stat3. This study aimed to identify the mechanism of Fbw7-mediated aerobic glycolysis reprogramming in DLBCL.
Methods
UNASSIGNED
Expression levels of Fbw7 and Lactate Dehydrogenase A (LDHA) in human DLBCL samples were evaluated by immunohistochemistry. Crosstalk between Fbw7 and LDHA signaling was analyzed by co-immunoprecipitation, ubiquitination assay, western blotting and mRNA quanlitative analyses.
Results
UNASSIGNED
Fbw7 could interact with LDHA to trigger its ubiquitination and degradation. Inversely, lactate negatively regulated Fbw7
Conclusions
UNASSIGNED
We demonstrated that the ubiquitin-ligase Fbw7 played a key role in LDHA-related aerobic glycolysis reprogramming in DLBCL. Our study uncovers a negative functional loop consisting of a Fbw7-mediated LDHA/lactate/miR-223 axis, which may support the future ABC-DLBCL therapy by targeting LDHA-related inhibition.
Identifiants
pubmed: 35359405
doi: 10.3389/fonc.2022.842356
pmc: PMC8960958
doi:
Types de publication
Journal Article
Langues
eng
Pagination
842356Informations de copyright
Copyright © 2022 Yao, Guo, Zhang, Chen, Xu, Luo, Luo, Lin, Chen, Li and Liu.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Références
J Cancer Res Clin Oncol. 2012 May;138(5):763-74
pubmed: 22270966
Curr Drug Targets. 2013 Sep;14(10):1150-6
pubmed: 23834147
Cancer Lett. 2019 Jun 1;451:136-141
pubmed: 30878527
Nat Commun. 2020 Jan 7;11(1):36
pubmed: 31911580
Nat Rev Cancer. 2017 Dec;17(12):707
pubmed: 29077692
J Exp Clin Cancer Res. 2017 Jan 10;36(1):10
pubmed: 28069035
Blood. 2016 Jun 9;127(23):2856-66
pubmed: 26941399
Cancer Cell. 2012 Oct 16;22(4):547-60
pubmed: 23079663
Mol Cell. 2020 Sep 17;79(6):1008-1023.e4
pubmed: 32871104
Nat Rev Cancer. 2016 Nov;16(11):694-707
pubmed: 27634449
Oncogene. 2012 Apr 5;31(14):1835-44
pubmed: 21860413
Cancer Lett. 2015 Mar 1;358(1):1-7
pubmed: 25528630
Cancer Res. 2015 Apr 1;75(7):1181-6
pubmed: 25716680
Cancer Biomark. 2017 Jul 4;19(4):353-363
pubmed: 28582845
Microrna. 2019;8(1):4-27
pubmed: 30147022
Cells. 2020 Jan 15;9(1):
pubmed: 31952362
Endocr Relat Cancer. 2010 Sep 23;17(4):R287-304
pubmed: 20699334
Clin Cancer Res. 2019 May 1;25(9):2809-2820
pubmed: 30728155
Blood. 2016 Dec 15;128(24):2797-2807
pubmed: 27737889
Semin Cancer Biol. 2016 Feb;36:52-61
pubmed: 26410034
J Clin Invest. 2018 Apr 2;128(4):1326-1337
pubmed: 29346117
J Exp Med. 2013 Jul 29;210(8):1545-57
pubmed: 23857984
Haematologica. 2018 Feb;103(2):288-296
pubmed: 29097500
J Clin Invest. 2020 Jul 1;130(7):3699-3716
pubmed: 32315286
Cancer Discov. 2015 Oct;5(10):1024-39
pubmed: 26382145
Mol Cell Biol. 2012 Jun;32(11):2160-7
pubmed: 22473991
FEBS J. 2012 Oct;279(20):3898-910
pubmed: 22897481
Am J Hematol. 2013 Jun;88(6):485-91
pubmed: 23512868
BioDrugs. 2017 Jun;31(3):275-278
pubmed: 28497220
Blood. 2017 Apr 27;129(17):2420-2428
pubmed: 28167662
Nat Med. 2015 Oct;21(10):1190-8
pubmed: 26366712
Am J Transl Res. 2016 Jun 15;8(6):2512-24
pubmed: 27398136
J Clin Invest. 2011 Jan;121(1):342-54
pubmed: 21123947
J Biol Chem. 2010 Nov 5;285(45):34439-46
pubmed: 20826802
Blood. 2020 Jun 4;135(23):2041-2048
pubmed: 32232482
Biochem Biophys Res Commun. 2018 Apr 15;498(4):869-876
pubmed: 29550488
Mol Cancer Ther. 2012 May;11(5):1122-32
pubmed: 22411899
Rev Bras Hematol Hemoter. 2013;35(3):189-91
pubmed: 23904809
Nat Commun. 2017 Jun 16;8:16000
pubmed: 28621309
Blood. 2016 Apr 7;127(14):1736-7
pubmed: 27056992
Lancet Haematol. 2016 Jul;3(7):e330-9
pubmed: 27374466
Nat Commun. 2018 Sep 3;9(1):3569
pubmed: 30177679
Oncotarget. 2014 Apr 30;5(8):2000-15
pubmed: 24899581
Oncotarget. 2015 Jan 30;6(3):1740-9
pubmed: 25638153
Mol Cell. 2007 Apr 13;26(1):131-43
pubmed: 17434132
Semin Cancer Biol. 2019 Aug;57:10-18
pubmed: 31009762
Cell. 2017 Oct 5;171(2):358-371.e9
pubmed: 28985563