食管癌;乙酰基转移酶;KAT2ASurvivin;乙酰化修饰," /> 食管癌;乙酰基转移酶;KAT2ASurvivin;乙酰化修饰,"/> Esophageal cancerAcetyltransferaseKAT2ASurvivinAcetylation modification,"/> <span style="font-family:宋体;font-size:10.5pt;">乙酰基转移酶</span><span style="font-family:'Times New Roman','serif';font-size:10.5pt;">KAT2A</span><span style="font-family:宋体;font-size:10.5pt;">和</span><span style="font-family:'Times New Roman','serif';font-size:10.5pt;">Survivin</span><span style="font-family:宋体;font-size:10.5pt;">蛋白乙酰化在食管癌中的相关性研究</span>

临床肿瘤学杂志 ›› 2023, Vol. 28 ›› Issue (01): 16-22.

• 论著 • 上一篇    

乙酰基转移酶KAT2ASurvivin蛋白乙酰化在食管癌中的相关性研究

  

  1.  067000  河北承德  承德医学院附属医院胸外科
  • 收稿日期:2022-06-22 修回日期:2022-10-12 出版日期:2023-01-31 发布日期:2023-03-08
  • 通讯作者: 孙光蕊 E-mail:93768910@qq.com
  • 基金资助:
     承德市科学技术研究与发展计划项目(201606A036);河北省医学科学研究重点课题计划项目(20210985

 Correlation of acetyltransferase KAT2A and survivin protein acetylation in esophageal cancer

  1. Department of Thoracic Surgery, Affiliated Hospital of Chengde Medical College
  • Received:2022-06-22 Revised:2022-10-12 Online:2023-01-31 Published:2023-03-08

摘要:  目的  探讨食管癌组织中乙酰基转移酶2AKAT2A)表达与Survivin蛋白乙酰化水平,分析二者在食管癌发生过程中的相关性。方法  选取70例食管鳞癌组织及其癌旁正常食管黏膜组织。实时荧光定量聚合酶链反应(qRT-PCR)检测SurvivinKAT2A mRNA的表达,免疫组化及Western blotting检测SurvivinKAT2A的蛋白表达,免疫荧光验证SurvivinKAT2A在癌组织中的定位及表达;免疫共沉淀检测Survivin乙酰化。分析Survivin蛋白乙酰化与KAT2A的相关性及其二者与食管癌临床病理特征的关系。构建KAT2A RNA干扰序列,脂质体介导法转染至食管癌EC109细胞。应用qRT-PCRWestern blotting检测转染siRNA-KAT2A 的食管癌EC109细胞中KAT2A mRNA和蛋白表达水平,免疫共沉淀检测EC109细胞中Survivin蛋白乙酰化水平。结果  食管癌组织中SurvivinKAT2A mRNA相对表达量高于癌旁组织(P<0.05);食管癌组织中SurvivinKAT2A蛋白呈高表达,而癌旁组织则呈低表达。免疫荧光证实SurvivinKAT2A蛋白在癌组织中同时呈现高表达状态,二者主要表达于细胞质中,部分表达于细胞核中。食管癌组织中Survivin蛋白发生了乙酰化,且食管癌组织中的乙酰化率显著高于癌旁组织(P0.05);在食管癌组织中Survivin乙酰化和KAT2A表达呈正相关(r=0.517P0.05);Survivin乙酰化和KAT2A表达与食管癌的TNM分期、分化程度和淋巴结转移有关(P0.05)。体外实验显示,RNA干扰下调KAT2A对食管癌细胞Survivin mRNA和蛋白表达量均无影响(P0.05),但Survivin蛋白的乙酰化水平显著降低(P0.05)。结论  在食管病变过程中KAT2A参与了Survivin乙酰化修饰,其高表达可能是Survivin乙酰化修饰重要的前期分子事件,在食管癌的诊治中具有潜在应用价值。

关键词:  , 食管癌;乙酰基转移酶;">食管癌;乙酰基转移酶;KAT2A">KAT2A">;Survivin">Survivin;乙酰化修饰">;乙酰化修饰')">">

Abstract:  Objective  To investigate the expression of acetyltransferase 2A (KAT2A) and survivin protein acetylation levels in esophageal cancer tissue, and to analyze the correlation and clinical significance during the onset of esophageal cancer. Methods  Seventy cases of esophageal squamous carcinoma tissues and adjacent cancer tissues were collected. The survivin and KAT2A mRNA expression was determined by reverse transcription and real-time PCR(qRT-PCR), the expression levels of survivin and KAT2A protein were detected by Immunohistochemistry and Western blotting. Fluorescence immunohistochemistry (IF) verified the location and expression of survivin and KAT2A in cancerous tissues.The survivin protein acetylation was detected by co-immunoprecipitation. The correlation between survivin protein acetylation and KAT2A, and the relationship between them and the clinicopathological characteristics of esophageal cancer were analyzed. KAT2A RNA interference sequences was constructed, then transfected into EC109 cells using liposome-mediated methods. qRT-PCR and Westrern blotting were used to detect the expression level of KAT2A mRNA and protein in esophageal cancer EC109 cells transfected with siRNA-KAT2A. The acetylation level of survivin protein was detected by co-immunoprecipitation. Results  The relative expression of survivin and KAT2A mRNA was higher in esophageal cancer tissues than that in adjacent cancer tissuesP0.05. Survivin and KAT2A protein were highly expressed in esophageal cancer tissues, whereas low expressed in adjacent cancer tissues. The survivin protein was acetylated in esophageal cancer tissues. Immunofluorescence confirmed that survivin and KAT2A protein both show a high expression state in cancer tissues, which are mainly expressed in the cytoplasm, partially expressed in the nucleus, and the acetylation rate was significantly higher than that in adjacent cancer tissuesP0.05. Survivin acetylation and KAT2A were related in esophageal cancer tissues, and it was positive correlationr=0.517, P0.05. Survivin protein acetylation and KAT2A are closely related to tumor TNM staging, differentiation grade and lymph node metastasisP0.05. The result of vitro experiments showed that there was no change in survivin mRNA and protein expression after downregulation of KAT2A by RNA interferenceP0.05, but the acetylation level of survivin protein was significantly reducedP0.05. Conclusion  Acetyltransferase KAT2A is involved in the survivin acetylation modification during the esophageal lesion. High expression of KAT2A may be an important molecular event of survivin acetylation modification and has potential value in the diagnosis and treatment of esophageal cancer.

Key words:  , Esophageal cancer">Esophageal cancer">;Acetyltransferase">Acetyltransferase">;KAT2A">KAT2A">;Survivin">Survivin">;Acetylation modification')">">Acetylation modification

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[1] 刘德龙, 蒋穗斌, 郭东铭. MALAT1靶向调控miR-205与骨肉瘤侵袭的实验研究[J]. 临床肿瘤学杂志, 2018, 23(5): 385-390.
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