磷酸化EZH2在头颈部鳞癌中的表达特征及对化疗敏感性的影响

Expression characteristics of phosphorylated EZH2 in head and neck squamous cell carcinoma and their effect on chemotherapy sensitivity

    摘要
  • 摘要:
      目的  探究头颈部鳞状细胞癌（head and neck squamous cell carcinoma，HNSCC）中磷酸化Zeste同源增强子（enhancer of Zeste homolog 2，EZH2）的表达特征及对化疗敏感性的影响。
      方法  选取2018年1月至2021年3月天津医科大学肿瘤医院HNSCC患者组织标本及临床资料53例。免疫组织化学染色分析HNSCC组织标本中p-EZH2S21、p-STAT3Y705、HIF-1α和Ki-67的表达水平。Western blot检测HNSCC组织和细胞株中p-EZH2S21的表达情况。在HNSCC细胞中构建EZH2野生型（EZH2-WT）和EZH2 S21位点突变（EZH2-S21A）的稳转细胞，CCK8实验和平板克隆实验检测EZH2以及S21位点磷酸化对HNSCC细胞增殖能力及其对顺铂（cisplatin，DDP）和5-氟尿嘧啶（5-fluorouracil，5-FU）敏感性的影响。
      结果  HNSCC中p-EZH2S21表达升高，并且与p-STAT3Y705（P<0.05），HIF-1α（P<0.01）表达呈正相关。临床特征相关性分析发现HNSCC中p-EZH2S21表达与淋巴结转移（P<0.000 5）、T分期（P<0.05）、N分期（P<0.000 1）和AJCC分期（P<0.05）呈正相关。体外实验证实EZH2表达促进 HNSCC细胞增殖能力并且抑制其对化疗的敏感性，抑制EZH2 S21磷酸化可以恢复肿瘤细胞对DDP和5-FU的敏感性。
      结论  p-EZH2S21在HNSCC肿瘤进展中具有重要作用，S21位点磷酸化是EZH2影响 HNSCC细胞增殖及其对化疗敏感性的重要途径。

     

    Abstract:
      Objective  To investigate the expression characteristics of phosphorylated enhancer of Zeste homolog 2 (EZH2) in head and neck squamous cell carcinoma (HNSCC) and their effect on chemosensitivity.
      Methods  Fifty-three patients with HNSCC treated between January 2018 and March 2021 in Tianjin Medical University Cancer Institute & Hospital were selected. Expression levels of p-EZH2S21, p-STAT3Y705, HIF-1α, and Ki-67 in HNSCC tissues were analyzed by immunohistochemical staining. Western blot was used to detect p-EZH2S21 expression in HNSCC tissues and cell lines. HNSCC cell lines stably transfected with wild type (EZH2-WT) or S21 mutant EZH2 (EZH2-S21A) were constructed. CCK8 and colony formation assays were performed to detect the effect of EZH2 and S21 phosphorylation on HNSCC cell proliferation and their sensitivity to cisplatin (DDP) and 5-fluorouracil (5-FU).
      Results   Elevated levels of p-EZH2S21 were observed in HNSCC tissues and positively correlated with p-STAT3Y705 (P<0.05) and HIF-1α (P<0.01) levels. p-EZH2S21 level correlated positively with lymph node metastasis (P<0.000 5), T (P<0.05), N (P<0.000 1) and AJCC stages (P<0.05). In vitro experiments confirmed that EZH2 expression promoted cell proliferation and attenuated chemosensitivity of HNSCC cells. Inhibition of p-EZH2S21 restored HNSCC cell sensitivity to DDP and 5-FU.
      Conclusions   p-EZH2S21 plays an important role in tumor progression in HNSCC, and phosphorylation at S21 is an important way for EZH2 to affect HNSCC cell proliferation and chemotherapy sensitivity.

     

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