Heterozygous IDH1R132H/WT created by "single base editing" inhibits human astroglial cell growth by downregulating YAP.

Oncogene
Shuang WeiShuli Xia

Abstract

Mutations in the isocitrate dehydrogenase 1 (IDH1) gene have been identified in a number of cancer types, including brain cancer. The Cancer Genome Atlas project has revealed that IDH1 mutations occur in 70-80% of grade II and grade III gliomas. Until recently, most of the functional studies of IDH1 mutations in cellular models have been conducted in overexpression systems with the IDH1 wild type background. In this study, we employed a modified CRISPR/Cas9 genome editing technique called "single base editing", and efficiently introduced heterozygous IDH1 R132H mutation (IDH1R132H/WT) in human astroglial cells. Global DNA methylation profiling revealed hypermethylation as well as hypomethylation induced by IDH1R132H/WT. Global gene expression analysis identified molecular targets and pathways altered by IDH1R132H/WT, including cell proliferation, extracellular matrix (ECM), and cell migration. Our phenotype analysis indicated that compared with IDH1 wild type cells, IDH1R132H/WT promoted cell migration by upregulating integrin β4 (ITGB4); and significantly inhibited cell proliferation. Using our mutated IDH1 models generated by "single base editing", we identified novel molecular targets of IDH1R132H/WT, namely Yes-associated p...Continue Reading

References

Feb 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·E O MajorJ Sever
Feb 1, 2008·Molecular Cancer Research : MCR·Thomas E ReznikJohn Laterra
Sep 6, 2008·Science·D Williams ParsonsKenneth W Kinzler
Feb 21, 2009·The New England Journal of Medicine·Hai YanDarell D Bigner
Feb 28, 2009·The American Journal of Pathology·Takuya WatanabeHiroko Ohgaki
Apr 21, 2009·International Journal of Cancer. Journal International Du Cancer·Mi Ran KangSug Hyung Lee
Aug 7, 2009·The New England Journal of Medicine·Elaine R MardisTimothy J Ley
Apr 30, 2010·Neurology·M LabussièreM Sanson
Oct 29, 2010·Genome Biology·Simon Anders, Wolfgang Huber
Dec 15, 2011·Neuro-oncology·H Artee LuchmanSamuel Weiss
Feb 18, 2012·The Journal of Biological Chemistry·Wesley M KonsavageGregory S Yochum
Oct 30, 2012·Bioinformatics·Alexander DobinThomas R Gingeras
Sep 21, 2013·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Michael W FerenczyEugene O Major
Dec 24, 2013·Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·Jinlong ShiJian Chen
Jan 5, 2014·Brain Tumor Pathology·Hemragul SabitJun-ichiro Hamada
Feb 18, 2014·Journal of Cell Science·Barry M Gumbiner, Nam-Gyun Kim
Sep 28, 2014·Bioinformatics·Simon AndersWolfgang Huber
Sep 30, 2014·Nature Methods·Yassen AssenovChristoph Bock
Jan 17, 2015·Nature Reviews. Cancer·Toshiro MoroishiKun-Liang Guan
Dec 25, 2015·Nature·William A FlavahanBradley E Bernstein
Feb 11, 2016·The International Journal of Biochemistry & Cell Biology·Daming CuiLiang Gao
Nov 8, 2016·Nature Cell Biology·Yekaterina A MiroshnikovaValerie M Weaver
Oct 12, 2017·Cell Reports·Sagar R ShahAlfredo Quiñones-Hinojosa

❮ Previous
Next ❯

Citations

May 28, 2019·Human Mutation·Jinling TangTao Sun
Oct 7, 2020·Journal of Clinical Pathology·Wei SangWei Zhang
Nov 23, 2020·Cell Death & Disease·Narges Zare MehrjardiUlf Dietrich Kahlert
Mar 9, 2021·Neuro-oncology Advances·Alex Shimura YamashitaGregory J Riggins
Mar 15, 2021·Biochemical and Biophysical Research Communications·Na ZhangWenzhe Ma
Feb 26, 2019·Molecular Pharmaceutics·Sagar R ShahAlfredo Quinones-Hinojosa
Oct 16, 2021·Journal of Cell Science·Shruti PatrickEllora Sen
Dec 25, 2021·Neuro-oncology·Chengchen HuYunqing Li

❮ Previous
Next ❯

Datasets Mentioned

BETA
GPL21145
GSE103558
GSE103557

Methods Mentioned

BETA
PCR
methylation
Chip
RNA-seq
FCS
transfection
methylation profiling
protein collection
Protein Assay
flow cytometry

Software Mentioned

RnBeads
HTSeq
GSEA
Axiovision
Prizm
DESeq
GraphPad
STAR
CellQuest

Related Concepts

Related Feeds

Cell Migration in Cancer and Metastasis

Migration of cancer cells into surrounding tissue and the vasculature is an initial step in tumor metastasis. Discover the latest research on cell migration in cancer and metastasis here.

CRISPR Ribonucleases Deactivation

CRISPR-Cas system enables the editing of genes to create or correct mutations. This feed focuses on mechanisms that underlie deactivation of CRISPR ribonucleases. Here is the latest research.

Astrocytes & Neurodegeneration

Astrocytes are important for the health and function of the central nervous system. When these cells stop functioning properly, either through gain of function or loss of homeostatic controls, neurodegenerative diseases can occur. Here is the latest research on astrocytes and neurodegeneration.

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.

CRISPR (general)

Clustered regularly interspaced short palindromic repeats (CRISPR) are DNA sequences in the genome that are recognized and cleaved by CRISPR-associated proteins (Cas). CRISPR-Cas system enables the editing of genes to create or correct mutations. Discover the latest research on CRISPR here.

CRISPR for Genome Editing

Genome editing technologies enable the editing of genes to create or correct mutations. Clustered regularly interspaced short palindromic repeats (CRISPR) are DNA sequences in the genome that are recognized and cleaved by CRISPR-associated proteins (Cas). Here is the latest research on the use of CRISPR-Cas system in gene editing.

CRISPR in Cancer

CRISPR-Cas system enables the editing of genes to create or correct mutations. Given that genome instability and mutation is one of the hallmarks of cancer, the CRISPR-Cas system is being explored to genetically alter and eliminate cancer cells. Here is the latest research.

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.

Astrocytes

Astrocytes are glial cells that support the blood-brain barrier, facilitate neurotransmission, provide nutrients to neurons, and help repair damaged nervous tissues. Here is the latest research.