Jumonji and AT-Rich Interacting Domain 2 (JARID2) exhibits a tumor-suppressive role in Oral Squamous Cell Carcinoma by modulating tumor progression and metastasis.

Unlabelled: Jumonji and AT Rich Interacting Domain2 (JARID2), a pivotal accessory component of Polycomb Repressive Complex 2 (PRC2) is a critical factor in cancer development. The objective of the study was to determine the role of JARID2 in Oral Squamous Cell Carcinoma (OSCC). RT-PCR, qRT-PCR, immunofluorescence, immunohistochemistry, and western blot were used to analyze the gene and protein expression in OSCC clinical samples and OSCC cell lines. The experiments have collectively demonstrated the downregulation of JARID2 mRNA and protein expression during OSCC metastasis. The cytoplasmic localization of JARID2 in OSCC tissues and cell lines were also observed. In addition, JARID2 was knocked down in HSC-3 cells by performing siRNA-mediated transfection which revealed an increase in the expression of mesenchymal markers, N-cadherin and vimentin, and a downregulation of epithelial marker E-cadherin. Moreover, silencing JARID2 significantly increased the metastatic features such as migration, invasion, and colony-formation ability in HSC-3 cells. Also, the knockdown significantly reduced the number of apoptotic cells, suggesting that JARID2 knockdown has critically promoted HSC-3 cell metastasis by enhancing the mesenchymal markers. Taken together, the study has confirmed that JARID2 acts as a tumor suppressor, the downregulation of which promotes OSCC progression by regulating Epithelial-to-Mesenchymal Transition (EMT).

Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-024-04163-8.