Sreeshma Bhuvanadas, Mohan A Mathan, Devi Arikketh
Stem Cell Biology and Cancer Biology Laboratory, Department of Genetic Engineering, School of Bioengineering, SRM Institute of Science and Technology, Chengalpattu District, Kattankulathur, Tamilnadu 603203 India.
Department of Oral and Maxillofacial Surgery, Karpaga Vinayaga Institute of Dental Sciences, Kancheepuram, 603308 India.
3 Biotech. 2024 Dec;14(12):319. doi: 10.1007/s13205-024-04163-8. Epub 2024 Nov 29.
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).
The online version contains supplementary material available at 10.1007/s13205-024-04163-8.
Jumonji和富含AT序列相互作用结构域2（JARID2）是多梳抑制复合物2（PRC2）的关键辅助成分，是癌症发展中的关键因素。本研究的目的是确定JARID2在口腔鳞状细胞癌（OSCC）中的作用。采用逆转录-聚合酶链反应（RT-PCR）、实时定量RT-PCR、免疫荧光、免疫组织化学和蛋白质免疫印迹法分析OSCC临床样本和OSCC细胞系中的基因和蛋白表达。这些实验共同证明了JARID2 mRNA和蛋白表达在OSCC转移过程中下调。还观察到JARID2在OSCC组织和细胞系中的细胞质定位。此外，通过小干扰RNA（siRNA）介导的转染在HSC-3细胞中敲低JARID2，结果显示间充质标志物N-钙黏蛋白和波形蛋白的表达增加，而上皮标志物E-钙黏蛋白的表达下调。此外，沉默JARID2显著增加了HSC-3细胞的迁移、侵袭和集落形成能力等转移特征。而且，敲低显著减少了凋亡细胞的数量，这表明敲低JARID2通过增强间充质标志物关键地促进了HSC-3细胞转移。综上所述，该研究证实JARID2作为一种肿瘤抑制因子，其下调通过调节上皮-间质转化（EMT）促进OSCC进展。
在线版本包含可在10.1007/s13205-024-04163-8获取的补充材料。
