Abstract

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.

Original languageEnglish
Pages (from-to)36-45
Number of pages10
JournalCancer Letters
Volume368
Issue number1
DOIs
Publication statusPublished - Nov 1 2015

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Radiation Tolerance
Squamous Cell Carcinoma
Carcinoma
Radiotherapy
Neoplastic Stem Cells
lissamine rhodamine B
Cell Line
Neoplasms
Mouth Neoplasms
Therapeutic Uses
Therapeutics
Epigenomics
Wound Healing
Radiation
Messenger RNA
Mortality

Keywords

  • Cancer stem cell
  • Head and neck cancer
  • JARID1B
  • Oral cancer
  • Radiotherapy
  • ShJARID1B

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Silencing JARID1B suppresses oncogenicity, stemness and increases radiation sensitivity in human oral carcinoma. / Lin, Chun Shu; Lin, Ying-Chin; Adebayo, Bamodu Oluwaseun; Wu, Alexander; Chen, Jia Hong; Peng, Yi Jen; Cheng, Ming Fang; Lee, Wei Hwa; Hsiao, Michael; Chao, Tsu Yi; Yeh, Chi-Tai.

In: Cancer Letters, Vol. 368, No. 1, 01.11.2015, p. 36-45.

Research output: Contribution to journalArticle

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title = "Silencing JARID1B suppresses oncogenicity, stemness and increases radiation sensitivity in human oral carcinoma",
abstract = "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.",
keywords = "Cancer stem cell, Head and neck cancer, JARID1B, Oral cancer, Radiotherapy, ShJARID1B",
author = "Lin, {Chun Shu} and Ying-Chin Lin and Adebayo, {Bamodu Oluwaseun} and Alexander Wu and Chen, {Jia Hong} and Peng, {Yi Jen} and Cheng, {Ming Fang} and Lee, {Wei Hwa} and Michael Hsiao and Chao, {Tsu Yi} and Chi-Tai Yeh",
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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

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.

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KW - Radiotherapy

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