TY - JOUR
T1 - CRISPR/Cas9 genome editing of epidermal growth factor receptor sufficiently abolished oncogenicity in anaplastic thyroid cancer
AU - Huang, Li Chi
AU - Tam, Ka Wai
AU - Liu, Wei Ni
AU - Lin, Chun-Yu
AU - Hsu, Kai Wen
AU - Hsieh, Wen Shyang
AU - Chi, Wei Ming
AU - Lee, Ai Wei
AU - Yang, Jinn-Moon
AU - Lin, Ching Ling
AU - Lee, Chia Hwa
PY - 2018/4/12
Y1 - 2018/4/12
N2 - 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 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.
AB - 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 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.
UR - http://www.scopus.com/inward/record.url?scp=85053893373&partnerID=8YFLogxK
U2 - 10.1155/2018/3835783
DO - 10.1155/2018/3835783
M3 - Article
C2 - 29849821
AN - SCOPUS:85053893373
SN - 0278-0240
VL - 2018
SP - 1
EP - 15
JO - Disease markers
JF - Disease markers
M1 - 3835783
ER -
