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

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  • Li-Chi Huang
    Department of Endocrinology and Metabolism, Cathay General Hospital, Taipei, Taiwan
  • Ka-Wai Tam
    Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan
  • Wei-Ni Liu
    Graduate Institute of Medical Science, College of Medicine, Taipei Medical University, Taipei, Taiwan
  • Chun-Yu Lin
    Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsinchu, Taiwan
  • Kai-Wen Hsu
    Research Center for Tumor Medical Science, China Medical University, Taichung, Taiwan
  • Wen-Shyang Hsieh
    Department of Laboratory Medicine, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan
  • Wei-Ming Chi
    Department of Laboratory Medicine, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan
  • Ai-Wei Lee
    Department of Anatomy and Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
  • Jinn-Moon Yang
    Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsinchu, Taiwan
  • Ching-Ling Lin
    Department of Endocrinology and Metabolism, Cathay General Hospital, Taipei, Taiwan
  • Chia-Hwa Lee
    Department of Laboratory Medicine, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan

Bibliographic Information

Published
2018
Resource Type
journal article
Rights Information
  • http://creativecommons.org/licenses/by/4.0/
DOI
  • 10.1155/2018/3835783
Publisher
Wiley

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Description

<jats:p>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 (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mi>P</mml:mi><mml:mo>=</mml:mo><mml:mn>0.017</mml:mn></mml:math> in CCLE and <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M2"><mml:mi>P</mml:mi><mml:mo>=</mml:mo><mml:mn>0.001</mml:mn></mml:math> 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 gene. To conclude, this study provides potential ATC therapeutic strategies for current and future clinical needs, which may be possible in increasing the survival rate of ATC patients by translational medicine.</jats:p>

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