Han Yanyan, Liu Dandan, Li Lianhong
Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1, Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.
The Fourth Medical Center of The General Hospital of the Chinese People's Liberation Army, Beijing, 100048, China.
Cancer Cell Int. 2021 Nov 4;21(1):592. doi: 10.1186/s12935-021-02287-y.
As an important component of the Hippo pathway, WW domain-containing transcription regulator 1 (TAZ), is a transcriptional coactivator that is responsible for the progression of various types of cancers. Programmed cell death protein 1 (PD-1) receptors in activated T cells and their ligand programming death force 1 (PD-L1) are the main checkpoint signals that control T cell activity. Studies have shown high levels of PD-L1 in various cancers and that PD-L1/PD-1 signals to evade T-cell immunity. Recent data have demonstrated that TAZ can regulate the characteristics of cancer cells via PD-L1. Cervical cancer is a common gynecological disease worldwide. In this study, we attempted to evaluate the effects of TAZ and PD-L1 on cervical cancer.
Hela cervical cancer cells were transfected with TAZ plasmid or TAZ siRNA or PD-L1 siRNA by using Lipofectamine 2000. The relationship between TAZ and PD-L1 in cervical cancer cells was determined by qRT-PCR and western blotting. The functional roles of TAZ were confirmed via CCK-8, Transwell and flow cytometry assays. Western blotting was utilized to observe the expression of BCL-2 and Caspase-3. The clinicopathological correlation of TAZ and PD-L1 was evaluated via relevant databases.
TAZ is upregulated in cervical cancer and induces the growth and metastasis of cervical cancer cells by targeting PD-L1and inhibiting the ratio of apoptotic of cancer cells. High TAZ and PD-L1 expression was observed in different stage, grade, histological patterns, and ages of cervical cancer groups compared with normal cervix groups. Furthermore, high TAZ expression was positively correlated with the infiltration levels of immune cells and the expression of PD-L1.
含WW结构域的转录调节因子1（TAZ）作为Hippo信号通路的重要组成部分，是一种转录共激活因子，与多种癌症的进展相关。活化T细胞中的程序性细胞死亡蛋白1（PD-1）受体及其配体程序性死亡配体1（PD-L1）是控制T细胞活性的主要检查点信号。研究表明，多种癌症中PD-L1水平较高，且PD-L1/PD-1信号可逃避T细胞免疫。最近的数据表明，TAZ可通过PD-L1调节癌细胞的特性。宫颈癌是全球常见的妇科疾病。在本研究中，我们试图评估TAZ和PD-L1对宫颈癌的影响。
使用Lipofectamine 2000将TAZ质粒或TAZ siRNA或PD-L1 siRNA转染至Hela宫颈癌细胞。通过qRT-PCR和蛋白质免疫印迹法确定宫颈癌细胞中TAZ与PD-L1的关系。通过CCK-8、Transwell和流式细胞术检测证实TAZ的功能作用。利用蛋白质免疫印迹法观察BCL-2和Caspase-3的表达。通过相关数据库评估TAZ和PD-L1的临床病理相关性。
TAZ在宫颈癌中上调，通过靶向PD-L1并抑制癌细胞凋亡比例来诱导宫颈癌细胞的生长和转移。与正常宫颈组相比，在宫颈癌组的不同分期、分级、组织学类型和年龄中均观察到TAZ和PD-L1的高表达。此外，TAZ高表达与免疫细胞浸润水平和PD-L1表达呈正相关。
