CRISPR/Cas9 Genome Editing of Epidermal Growth Factor Receptor Sufficiently Abolished Oncogenicity in Anaplastic Thyroid Cancer

Disease Markers
Li-Chi HuangChia-Hwa Lee

Abstract

Anaplastic carcinoma of the thyroid (ATC), also called undifferentiated thyroid cancer, is the least common but most aggressive and deadly thyroid gland malignancy of all thyroid cancers. The aim of this study is to explore essential biomarker and use CRISPR/Cas9 with lentivirus delivery to establish a gene-target therapeutic platform in ATC cells. At the beginning, the gene expression datasets from 1036 cancers from CCLE and 8215 tumors from TCGA were collected and analyzed, showing EGFR is predominantly overexpressed in thyroid cancers than other type of cancers (P = 0.017 in CCLE and P = 0.001 in TCGA). Using CRISPR/Cas9 genomic edit system, ATC cells with EGFR sgRNA lentivirus transfection obtained great disruptions on gene and protein expression, resulting in cell cycle arrest, cell growth inhibition, and most importantly metastasis turn-off ability. In addition, the FDA-approved TKI of afatinib for EGFR targeting also illustrates great anticancer activity on cancer cell death occurrence, cell growth inhibition, and cell cycle arrest in SW579 cells, an EGFR expressing human ATC cell line. Furthermore, off-target effect of using EGFR sgRNAs was measured and found no genomic editing can be detected in off-target candidate ge...Continue Reading

References

Oct 1, 1994·Annals of Oncology : Official Journal of the European Society for Medical Oncology·F OrlandiA Angeli
Aug 16, 1994·Proceedings of the National Academy of Sciences of the United States of America·P M GuyK L Carraway
Mar 2, 2005·Cancer·Electron KebebewAlex McMillan
Jul 11, 2006·The Journal of Clinical Endocrinology and Metabolism·Constantine S MitsiadesNicholas Mitsiades
Apr 14, 2007·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Fumihiko MitsuiAkishi Ooi
Sep 18, 2008·The Journal of Pathology·Y TsukamotoM Moriyama
Sep 25, 2009·Endocrine-related Cancer·Cristina Rodríguez-AntonaMercedes Robledo
Mar 20, 2010·The Cochrane Database of Systematic Reviews·Aihua TanYunfei Cao
Apr 27, 2010·Clinical Oncology : a Journal of the Royal College of Radiologists·R C Smallridge, J A Copland
Nov 20, 2012·Surgery·Electron Kebebew
Apr 10, 2013·Genome Research·Marion PiganeauErika Brunet
Jun 19, 2013·Clinical Lung Cancer·Elsa VanheckeKen A Olaussen
Aug 29, 2013·Drugs·Rosselle T Dungo, Gillian M Keating
Sep 5, 2013·Molecular Therapy : the Journal of the American Society of Gene Therapy·Wei HeJohn F Boylan
Sep 10, 2013·Proceedings of the National Academy of Sciences of the United States of America·Ryan M Walsh, Konrad Hochedlinger
Sep 12, 2013·Clinical Chemistry and Laboratory Medicine : CCLM·Dorte Aa OlsenIvan Brandslund
Dec 18, 2013·Science·Ophir ShalemFeng Zhang
Dec 18, 2013·Clinical & Experimental Metastasis·Sabrina Daniela SilvaLuiz Paulo Kowalski
Jan 11, 2014·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Heae Surng ParkSo Yeon Park
Apr 1, 2014·Nature Biotechnology·Hao YinDaniel G Anderson
Jul 30, 2014·Cancer Research·Shuyuan ZhangHao Zhu
Jul 31, 2014·Nature Methods·Neville E SanjanaFeng Zhang
Jan 24, 2015·Science·Mathias UhlénFredrik Pontén
Aug 19, 2015·PloS One·Yupeng CaiWensheng Hou
Jun 1, 2016·Lancet·Maria E CabanillasCosimo Durante
Dec 3, 2016·Nature·Mehdi BouhaddouMarc R Birtwistle

❮ Previous
Next ❯

Citations

Mar 30, 2019·Thyroid : Official Journal of the American Thyroid Association·Xinyi CaoYupeng Chen
Oct 1, 2019·British Journal of Cancer·Alessandro LeonettiMarcello Tiseo
May 11, 2019·International Journal of Molecular Sciences·Shu-Huey ChenChia-Hwa Lee

❮ Previous
Next ❯

Methods Mentioned

BETA
flow cytometry
Polymerase Chain Reaction
PCR
electrophoresis
transfection
Assay
gene knockout

Software Mentioned

ImageJ
TIDE
SigmaPlot
Roche LightCycler
Statistical Package for the Social Sciences
Tracking by Decomposition ( TIDE )

Related Concepts

Related Feeds

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.

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.

Cancer Genomics (Keystone)

Cancer genomics approaches employ high-throughput technologies to identify the complete catalog of somatic alterations that characterize the genome, transcriptome and epigenome of cohorts of tumor samples. Discover the latest research using such technologies in this feed.