BMP8A promotes survival and drug resistance via Nrf2/TRIM24 signaling pathway in clear cell renal cell carcinoma.

Cancer Science
Yi-Peng YuCheng Zhang

Abstract

There is increasing evidence that bone morphogenetic proteins (BMP) are involved in the proliferation and drug tolerance of kidney cancer. However, the molecular mechanism of BMP8A in renal cell proliferation and drug tolerance is not clear. Here we showed that BMP8A was highly expressed in renal cell carcinoma, which suggests a poor prognosis of ccRCC. Promotion of cell proliferation and inhibition of apoptosis were detected by CCK-8 assay, Trypan Blue staining, flow cytometry and bioluminescence. BMP8A promoted resistance of As2 O3 by regulating Nrf2 and Wnt pathways in vitro and in vivo. Mechanistically, BMP8A enhanced phosphorylation of Nrf2, which, in turn, inhibited Keap1-mediated Nrf2 ubiquitination and, ultimately, promoted nuclear translocation and transcriptional activity of Nrf2. Nrf2 regulates the transcription of TRIM24 detected by ChIP-qPCR. BMP8A was highly expressed in ccRCC, which suggests a poor prognosis. BMP8A was expected to be an independent prognostic molecule for ccRCC. On the one hand, activated Nrf2 regulated reactive oxygen balance, and on the other hand, by regulating the transcription level of TRIM24, it was involved in the regulation of the Wnt pathway to promote the proliferation, invasion and met...Continue Reading

References

Nov 23, 2000·Nature·T Finkel, N J Holbrook
Oct 21, 2010·Cellular Signalling·Beth BragdonAnja Nohe
Dec 18, 2010·Nature·Wen-Wei TsaiMichelle Craig Barton
May 3, 2011·Proceedings of the National Academy of Sciences of the United States of America·Benjamin HerquelRégine Losson
Oct 8, 2011·Nature Reviews. Cancer·Shigetsugu Hatakeyama
Jan 31, 2012·Cellular Signalling·Paul D RayYoshiaki Tsuji
Feb 2, 2012·Breast Cancer Research : BCR·Oriana E Hawkins, Ann Richmond
Apr 5, 2013·Anti-cancer Drugs·Sebastiano ButiFrancesco Massari
Dec 25, 2013·International Journal of Oncology·Hong-Quan DuongInsoo Bae
May 2, 2014·European Journal of Pharmacology·Sina KardehAli Mohammad Alizadeh
Jul 12, 2014·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Young-Sam Keum, Bu Young Choi
Apr 3, 2016·Cancer Letters·Sahdeo PrasadAmit K Tyagi
Apr 14, 2016·Cancer Cell·Christopher J RickettsW Marston Linehan
May 31, 2016·Cancer Cell·Anna C GronerMyles Brown
Oct 23, 2016·Drug Discovery Today. Technologies·Srikanth AppikondaMichelle Craig Barton
Jan 16, 2017·Free Radical Biology & Medicine·Sehamuddin GaladariFaisal Thayyullathil
Oct 28, 2017·Cancer Research·Vaidehi KrishnanYoshiaki Ito
Nov 14, 2017·Nature Communications·Deguan LvHaizhong Feng
Apr 17, 2018·Cell·Samra TurajlicUNKNOWN TRACERx Renal Consortium

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Citations

Oct 3, 2020·Molecular Cancer·Tianshui SunQing Yang
Nov 26, 2020·Cancers·Sara Clerici, Alessandra Boletta

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Datasets Mentioned

BETA
GSE53757

Methods Mentioned

BETA
surgical resection
nuclear translocation
xenograft
transfection
PCR
Assay
ELISA
ubiquitination
immunoprecipitation
ChIP

Software Mentioned

GSEA
GraphPad

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