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.

Cancer Letters
|July 18, 2015
PubMed
Abstract

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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