The CUL4B-miR-372/373-PIK3CA-AKT axis regulates metastasis in bladder cancer.

Oncogene
Xiaochen LiuYaoqin Gong

Abstract

CUL4B, which acts as a scaffold protein in CUL4B-RING ubiquitin ligase (CRL4B) complexes, participates in a variety of biological processes. Previous studies have shown that CUL4B is often overexpressed and exhibits oncogenic activities in a variety of solid tumors. However, the roles and the underlying mechanisms of CUL4B in bladder cancer (BC) were poorly understood. Here, we showed that CUL4B levels were overexpressed and positively correlated with the malignancy of BC, and CUL4B could confer BC cells increased motility, invasiveness, stemness, and chemoresistance. The PIK3CA/AKT pathway was identified as a critical downstream mediator of CUL4B-driven oncogenicity in BC cells. Furthermore, we demonstrated that CRL4B epigenetically repressed the transcription of miR-372/373, via catalyzing monoubiquitination of H2AK119 at the gene cluster encoding miR-372/373, leading to upregulation of PIK3CA and activation of AKT. Our findings thus establish a critical role for the CUL4B-miR-372/373-PIK3CA/AKT axis in the pathogenesis of BC and have important prognostic and therapeutic implications in BC.

References

May 1, 1973·International Journal of Cancer. Journal International Du Cancer·J BubeníkJ Donner
May 29, 1997·International Journal of Cancer. Journal International Du Cancer·Y ZhangK Esuvaranathan
Jul 3, 2002·Nature Reviews. Cancer·Igor Vivanco, Charles L Sawyers
Mar 16, 2004·Science·Yardena SamuelsVictor E Velculescu
Dec 13, 2005·Nature Reviews. Drug Discovery·Bryan T HennessyGordon B Mills
May 14, 2008·Current Cancer Drug Targets·Amancio CarneroJuan F M Leal
Sep 27, 2008·Cell Cycle·Meng QiaoArthur B Pardee
Jul 4, 2009·Cancer Cell·Krishna M VasudevanLevi A Garraway
Oct 1, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Fiona M PlattMargaret A Knowles
Sep 4, 2012·Biochemical and Biophysical Research Communications·Qingbo Lang, Changquan Ling
Mar 13, 2013·The Journal of Cell Biology·Yongxin ZouYaoqin Gong
Oct 15, 2013·Nature Genetics·David A SolomonTodd Waldman
Jan 31, 2014·Nature·UNKNOWN Cancer Genome Atlas Research Network
Feb 4, 2014·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Qian-Qian YuLiang Chen
Jul 25, 2014·Therapeutic Advances in Medical Oncology·Elisavet Paplomata, Ruth O'Regan
Dec 24, 2014·Nature Reviews. Cancer·Margaret A Knowles, Carolyn D Hurst
Jul 1, 2015·Proceedings of the National Academy of Sciences of the United States of America·M Cecilia CainoDario C Altieri
Oct 17, 2015·Annual Review of Medicine·Ingrid A Mayer, Carlos L Arteaga
Apr 14, 2017·Nature Reviews. Disease Primers·Oner SanliYair Lotan
Apr 22, 2017·Cell·Brendan D Manning, Alex Toker
Oct 7, 2017·Nature Medicine·Eduard Batlle, Hans Clevers
Jan 5, 2019·The Prostate·Mingfeng ZhaoBo Han
Apr 17, 2019·Cancers·Alexander LangWolfgang A Schulz

❮ Previous
Next ❯

Citations

Nov 24, 2020·The International Journal of Biochemistry & Cell Biology·Shouzhen ChenBenkang Shi
May 20, 2021·Molecular Cancer·Lei LiuYongxin Zou
May 21, 2021·The Tohoku Journal of Experimental Medicine·Chao ZhangPei Liu

❮ Previous
Next ❯

Methods Mentioned

BETA
xenograft
RNA-Seq
transfection
ChIP
immunoprecipitation

Software Mentioned

GraphPad Prism
miRNAMap
IVIS
ImageJ
SPSS
Excel

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.