Methylation Status of the Nanog Promoter Determines the Switch between Cancer Cells and Cancer Stem Cells

Advanced Science
Shupeng LiuShanrong Liu

Abstract

Cancer stem cells (CSCs) are the main cause of tumor development, metastasis, and relapse. CSCs are thus considered promising targets for cancer therapy. However, it is hard to eradicate CSCs due to their inherent plasticity and heterogeneity, and the underlying mechanism of the switch between non-CSCs and CSCs remains unclear. Here, it is shown that miR-135a combined with SMYD4 activates Nanog expression and induces the switch of non-CSCs into CSCs. The miR-135a level, once elevated, lowers the methylation level of the CG5 site in the Nanog promoter by directly targeting DNMT1. SMYD4 binds to the unmethylated Nanog promoter to activate Nanog expression in Nanog-negative tumor cells. The in vivo regulation of miR-135a levels could significantly affect both the CSCs proportion and tumor progression. These findings indicate that DNA methylation of the Nanog promoter modulates the switch of non-CSCs into CSCs under the control of the miRNA-135 level. In addition, the related pathways, miR-135a/DNMT1 and SMYD4, involved in these processes are potential targets for CSC-targeted therapy.

References

Mar 12, 2003·Proceedings of the National Academy of Sciences of the United States of America·Muhammad Al-HajjMichael F Clarke
Mar 7, 2006·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Peter SzlosarekFrances R Balkwill
Sep 23, 2006·The New England Journal of Medicine·Craig T JordanMark Noble
Sep 12, 2008·Nature Reviews. Cancer·Jane E Visvader, Geoffrey J Lindeman
Apr 14, 2010·Cancer Cell·Ruihuan ChenHeidi S Phillips
Oct 12, 2010·Epigenetics : Official Journal of the DNA Methylation Society·Daniel NettersheimHubert Schorle
Apr 5, 2012·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Juanjuan ShanCheng Qian
Oct 25, 2012·The Journal of Clinical Investigation·Kyung Hee NohTae Woo Kim
Jan 18, 2013·Genome Research·Katherine E VarleyRichard M Myers
Mar 15, 2013·Medical Hypotheses·Yijun HuShanrong Liu
Mar 13, 2014·Cell Stem Cell·Antonija Kreso, John E Dick
Jun 18, 2014·Postȩpy higieny i medycyny doświadczalnej·Łukasz FuławkaAgnieszka Hałoń
Apr 25, 2015·Nature Communications·Rajneesh PathaniaMuthusamy Thangaraju
Aug 15, 2015·Cancer Letters·Zhuo ChengJin Ding
Sep 5, 2015·Cell Stem Cell·Michael D BrooksMax S Wicha
Oct 7, 2016·Science·Cristina Morales TorresPaola Scaffidi
Oct 25, 2016·Biochimica Et Biophysica Acta·Maximilian BoeschDominik Wolf
Feb 12, 2017·Cell·Nicholas McGranahan, Charles Swanton
Mar 25, 2017·Stem Cells International·Eunice Yuen-Ting LauTerence Kin-Wah Lee
Apr 7, 2017·Molecular Carcinogenesis·Shu-Chun TsaiSen-Yung Hsieh
Jun 24, 2017·Frontiers in Genetics·Bhavani P Madakashira, Kirsten C Sadler
Jul 19, 2017·Trends in Cancer·Elanor N Wainwright, Paola Scaffidi
Dec 18, 2018·Cell Stem Cell·Piyush B GuptaCharlotte Kuperwasser
Jan 1, 2019·Cell Stem Cell·Caner SayginJustin D Lathia

❮ Previous
Next ❯

Citations

Sep 23, 2020·Journal of Cellular Physiology·Basira NajafzadehBehzad Baradaran
Nov 17, 2020·International Journal of Cancer. Journal International Du Cancer·Rhiannon French, Siim Pauklin
Jan 10, 2021·Pharmacology & Therapeutics·Juntao LiErxi Wu
Mar 7, 2021·International Journal of Molecular Sciences·Hongni XueZekun Guo
Feb 19, 2021·Regenerative Therapy·Kosuke YoshidaTakahiro Ochiya

❮ Previous
Next ❯

Methods Mentioned

BETA
transfection
FACS
immunoprecipitation
pull down
ChIP
Transgenic
PCR

Software Mentioned

_ Analyzer
RNA22
SPSS
BiQ

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.