Zinc-finger protein 750 mitigates malignant biological behavior of oral CSC-like cells enriched from parental CAL-27 cells.
Zinc-finger protein 750 mitigates malignant biological behavior of oral CSC-like cells enriched from parental CAL-27 cells.
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锌指蛋白 750 可减轻从亲代 CAL-27 细胞中富集的口腔 CSC 样细胞的恶性生物学行为。
DOI：
10.3892/ol.2021.13146
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发表时间：
2021-11
期刊：
影响因子：
2.9
通讯作者：
Chen Hai-Ying
中科院分区：
文献类型：
--
作者：
Xu Cong;Yang Hong-Li;Yang Yi-Kun;Pan Li;Chen Hai-Ying
口腔鳞状细胞癌是最常见的口腔恶性肿瘤。已知癌症干细胞（CSC）负责癌症复发和转移。锌指蛋白750（ZNF 750）可抑制口腔鳞癌细胞的增殖和侵袭。本研究旨在阐明ZNF 750在抑制来自OSCC细胞系CAL-27的CSCs的更新能力中的作用。采用乙醛脱氢酶（ALDH）、肿瘤球形成和集落形成试验检测ZNF 750对CSC样特性的影响。采用逆转录-定量PCR和蛋白质印迹法检测八聚体结合转录因子4、性别决定区Y-box 2、zeste增强子同源物2（Ezh 2）、胚胎外胚层发育（EED）和SUZ 12多梳抑制复合物2亚基（SUZ 12）的表达水平，并筛选与转移相关的基因。ZNF 750可有效抑制CSC样细胞的自我更新能力，降低ALDH阳性细胞数、肿瘤球和集落形成能力、细胞活力和干细胞因子。此外，ZNF 750可降低Ezh 2、EED和SUZ 12的表达水平。ZNF 750抑制MMP 1、3、9和13的表达，降低细胞的侵袭和迁移能力。此外，基质金属蛋白酶组织抑制剂-1的表达增加ZNF 750。然而，在ZNF 750基因敲除后观察到相反的效果。总之，本研究表明，ZNF 750具有抑制从亲本CAL-27细胞富集的CSC样细胞更新的潜力。
Oral squamous cell carcinoma (OSCC) is the most commonly occurring oral malignancy. Cancer stem cells (CSCs) are known to be responsible for cancer recurrence and metastasis. Zinc-finger protein 750 (ZNF750) has been reported to inhibit OSCC cell proliferation and invasion. The present study aimed to elucidate the role of ZNF750 in the inhibition of the renewal ability of CSCs derived from the OSCC cell line, CAL-27. The effects of ZNF750 on CSC-like properties were examined using aldehyde dehydrogenase (ALDH), tumor sphere formation and colony formation assays. Reverse transcription-quantitative PCR and western blotting were performed to detect the expression levels of octamer-binding transcription factor 4, sex-determining region Y-box 2, the enhancer of zeste homolog 2 (Ezh2), embryonic ectoderm development (EED) and SUZ12 polycomb repressive complex 2 subunit (SUZ12), and for the identification of genes associated with metastasis. ZNF750 effectively attenuated CSC-like cell self-renewal abilities; ZNF750 decreased the ALDH-positive cell population, tumor sphere and colony formation abilities, cell viability and stemness factors. Furthermore, the expression levels of Ezh2, EED and SUZ12 were decreased by ZNF750. ZNF750 inhibited MMP1, 3, 9 and 13 expression levels, and decreased the cell invasion and migratory abilities. Moreover, the expression of tissue inhibitors of matrix metalloproteinases-1 was increased by ZNF750. However, opposite effects were observed following the knockdown of the ZNF750 gene. Overall, the present study demonstrated that ZNF750 has the potential to inhibit the renewal of CSC-like cells enriched from parental CAL-27 cells.