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Published on: May 11, 2016
Silencing JARID1B suppresses oncogenicity, stemness and increases radiation sensitivity in human oral carcinoma
Chun-Shu Lin1, Ying-Chin Lin2, Bamodu Oluwaseun Adebayo3
1Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
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.
Insights
Inhibiting JARID1B in oral squamous cell carcinoma (OSCC) reduces cancer cell migration, invasion, and stem cell activity. This inhibition potentiates radiotherapy, offering a potential therapeutic strategy for OSCC patients.
Area of Science:
- Oncology
- Epigenetics
- Cancer Biology
Background:
- Oral squamous cell carcinoma (OSCC) poses a significant global health challenge, with radiotherapy efficacy often compromised by radioresistance.
- JARID1B, an epigenetic factor, has demonstrated oncogenic potential across various cancer types, suggesting its role in OSCC progression.
Purpose of the Study:
- To investigate the impact of JARID1B inhibition on the migration and invasion capabilities of human OSCC cell lines.
- To assess the effect of JARID1B inhibition on oral cancer stem cell activity and its synergy with radiotherapy.
- To determine the prognostic relevance of JARID1B expression in OSCC patients.
Main Methods:
- Utilized wound healing, Matrigel invasion, and spheroid formation assays to evaluate OSCC cell behavior.
- Employed shJARID1B to inhibit JARID1B expression in OSCC cell lines.
- Analyzed the expression of key genes involved in cancer stemness and radioresistance.
- Correlated JARID1B expression levels with patient outcomes in a cohort of 81 OSCC patients.
Main Results:
- JARID1B inhibition significantly reduced migration, invasion, and spheroid formation in OSCC cell lines.
- Silencing JARID1B enhanced the tumor-inhibitory effects of radiation therapy in OSCC models.
- Knockdown of JARID1B prior to radiotherapy led to decreased mRNA levels of genes associated with cancer stemness and radioresistance (e.g., NRF2, OCT4, CD133).
- JARID1B overexpression was identified as a significant prognostic factor in OSCC patients.
Conclusions:
- JARID1B inhibition effectively suppresses OSCC cell migration, invasion, and stem cell characteristics.
- Combining JARID1B knockdown with radiotherapy presents a promising therapeutic strategy to improve treatment outcomes in OSCC.
- Targeting JARID1B may overcome radioresistance and enhance the efficacy of radiotherapy for oral cancer.
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