TY - JOUR
T1 - Silencing JARID1B suppresses oncogenicity, stemness and increases radiation sensitivity in human oral carcinoma
AU - Lin, Chun Shu
AU - Lin, Ying-Chin
AU - Adebayo, Bamodu Oluwaseun
AU - Wu, Alexander
AU - Chen, Jia Hong
AU - Peng, Yi Jen
AU - Cheng, Ming Fang
AU - Lee, Wei Hwa
AU - Hsiao, Michael
AU - Chao, Tsu Yi
AU - Yeh, Chi-Tai
N1 - Publisher Copyright:
© 2015 Elsevier Ireland Ltd.
PY - 2015/11/1
Y1 - 2015/11/1
N2 - Purpose: Oral squamous cell carcinoma (OSCC) is a major cause of human mortality globally and radiotherapy is one of the main treatment modalities, however its therapeutic effect is often limited by radioresistance. JARID1B is an epigenetic factor with reported oncogenic potential in various cancer types. We investigated the effect of JARID1B inhibition on migration and invasion of human OSCC cell lines, as well as on clinical patients' outcome. Materials and Methods: Wound healing, matrigel invasion, Sulforhodamine B, and spheroid formation assays were used to characterize the signaling pathways of shJARID1B in response to radiation treatment. We evaluated the prognostic relevance of Jarid1b expression in a cohort of 81 OSCC patients. Results: Human OSCC cell lines, including SAS, HSC3, Cal27, TW2.6 and SCC4 cells, were used. shJARID1B cells significantly inhibited migration and invasion ability compared to their vector or wild type counterparts. Silencing shJARID1B significantly inhibited oral cancer stem cell activity and potentiated the tumor-inhibitory activity of radiation therapy in OSCC. Radiotherapy coupled with shJARID1B knockdown reduced mRNA levels of NQO1, KEAP1, NRF2, FOXO1, FOXO3, KLF4, OCT4, CD133, and Nanog in malignant OSCC cells. OSCC spheroid formation ability was markedly reduced in the shJARID1B cells. JARID1B overexpression is a dependent prognostic factor in OSCC patients. Conclusions: Silencing shJARID1B inhibits migration and invasion of human OSCC, reduces cancer stem cell activities and potentiates tumor-inhibiting radiotherapeutic effects. JARID1B knockdown prior to radiotherapy is a potential effective therapeutic strategy for the treatment of OSCC.
AB - Purpose: Oral squamous cell carcinoma (OSCC) is a major cause of human mortality globally and radiotherapy is one of the main treatment modalities, however its therapeutic effect is often limited by radioresistance. JARID1B is an epigenetic factor with reported oncogenic potential in various cancer types. We investigated the effect of JARID1B inhibition on migration and invasion of human OSCC cell lines, as well as on clinical patients' outcome. Materials and Methods: Wound healing, matrigel invasion, Sulforhodamine B, and spheroid formation assays were used to characterize the signaling pathways of shJARID1B in response to radiation treatment. We evaluated the prognostic relevance of Jarid1b expression in a cohort of 81 OSCC patients. Results: Human OSCC cell lines, including SAS, HSC3, Cal27, TW2.6 and SCC4 cells, were used. shJARID1B cells significantly inhibited migration and invasion ability compared to their vector or wild type counterparts. Silencing shJARID1B significantly inhibited oral cancer stem cell activity and potentiated the tumor-inhibitory activity of radiation therapy in OSCC. Radiotherapy coupled with shJARID1B knockdown reduced mRNA levels of NQO1, KEAP1, NRF2, FOXO1, FOXO3, KLF4, OCT4, CD133, and Nanog in malignant OSCC cells. OSCC spheroid formation ability was markedly reduced in the shJARID1B cells. JARID1B overexpression is a dependent prognostic factor in OSCC patients. Conclusions: Silencing shJARID1B inhibits migration and invasion of human OSCC, reduces cancer stem cell activities and potentiates tumor-inhibiting radiotherapeutic effects. JARID1B knockdown prior to radiotherapy is a potential effective therapeutic strategy for the treatment of OSCC.
KW - Cancer stem cell
KW - Head and neck cancer
KW - JARID1B
KW - Oral cancer
KW - Radiotherapy
KW - ShJARID1B
UR - http://www.scopus.com/inward/record.url?scp=84939792925&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84939792925&partnerID=8YFLogxK
U2 - 10.1016/j.canlet.2015.07.003
DO - 10.1016/j.canlet.2015.07.003
M3 - Article
C2 - 26184998
AN - SCOPUS:84939792925
SN - 0304-3835
VL - 368
SP - 36
EP - 45
JO - Cancer Letters
JF - Cancer Letters
IS - 1
ER -