Lai Kuo-Chu, Regmi Prabha, Liu Chung-Ji, Lo Jeng-Fan, Lee Te-Chang
Department of Physiology and Pharmacology, College of Medicine, Chang Gung University, Taoyuan City 33302, Taiwan.
Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan City 33302, Taiwan.
Biomedicines. 2023 Mar 14;11(3):896. doi: 10.3390/biomedicines11030896.
(1) Background: Cancer stem cells (CSCs) are a small cell population associated with chemoresistance, metastasis and increased mortality rate in oral cancer. Interferon-induced proteins with tetratricopeptide repeats 2 (IFIT2) depletion results in epithelial to mesenchymal transition, invasion, metastasis, and chemoresistance in oral cancer. To date, no study has demonstrated the effect of IFIT2 depletion on the CSC-like phenotype in oral cancer cells. (2) Methods: Q-PCR, sphere formation, Hoechst 33,342 dye exclusion, immunofluorescence staining, and flow cytometry assays were performed to evaluate the expression of the CSC markers in IFIT2-depleted cells. A tumorigenicity assay was adopted to assess the tumor formation ability. Immunohistochemical staining was used to examine the protein levels of IFIT2 and CD24 in oral cancer patients. (3) Results: The cultured IFIT2 knockdown cells exhibited an overexpression of ABCG2 and CD44 and a downregulation of CD24 and gave rise to CSC-like phenotypes. Clinically, there was a positive correlation between IFIT2 and CD24 in the patients. IFIT2/CD24/CD44 expression profiles predicted a better prognosis in HNC, including oral cancer. The TNF-α blockade abolished the IFIT2 depletion-induced sphere formation, indicating that TNF-α may be involved in the CSC-like phenotypes in oral cancer. (4) Conclusions: The present study demonstrates that IFIT2 depletion promotes CSC-like phenotypes in oral cancer.
(1) 背景：癌症干细胞（CSCs）是一小部分与口腔癌的化疗耐药性、转移及死亡率增加相关的细胞群体。干扰素诱导的四肽重复序列蛋白2（IFIT2）缺失会导致口腔癌发生上皮-间质转化、侵袭、转移及化疗耐药。迄今为止，尚无研究证实IFIT2缺失对口腔癌细胞中癌症干细胞样表型的影响。(2) 方法：进行定量聚合酶链反应（Q-PCR）、成球实验、Hoechst 33342染料排除实验、免疫荧光染色及流式细胞术分析，以评估IFIT2缺失细胞中癌症干细胞标志物的表达。采用致瘤性实验评估肿瘤形成能力。免疫组织化学染色用于检测口腔癌患者中IFIT2和CD24的蛋白水平。(3) 结果：培养的IFIT2基因敲低细胞表现出ABCG2和CD44的过表达以及CD24的下调，并产生癌症干细胞样表型。临床上，患者中IFIT2和CD24之间存在正相关。IFIT2/CD24/CD44表达谱预测包括口腔癌在内的头颈部癌预后较好。肿瘤坏死因子-α（TNF-α）阻断消除了IFIT2缺失诱导的成球现象，表明TNF-α可能参与口腔癌的癌症干细胞样表型。(4) 结论：本研究表明IFIT2缺失促进口腔癌中的癌症干细胞样表型。
