解剖学报

解剖学报 ›› 2023, Vol. 54 ›› Issue (4): 425-433.doi: 10.16098/j.issn.0529-1356.2023.04.008

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MLLT1超伸长复合亚基在肝细胞癌发生发展中的作用及其临床意义

于华婧 魏路阳 刘姗姗 管成剑 张忠涛*   

  1. 首都医科大学附属北京友谊医院普外科，国家消化系统疾病临床医学研究中心，北京 100050
  • 收稿日期:2023-03-23 修回日期:2023-04-19 出版日期:2023-08-06 发布日期:2023-08-06
  • 通讯作者: 张忠涛 E-mail:zhangzht@ccmu.edu.cn
  • 基金资助:
    ZBTB16-MTA3/NuRD复合体抑制肝细胞癌肝癌侵袭与转移的分子机制研究;ACAT1的巴豆酰化修饰通过调控脂肪酸氧化影响非酒精性脂肪性肝病发生发展的分子机制研究;CPT2的巴豆酰化修饰通过调控脂肪酸β氧化驱动非酒精性脂肪性肝病发生的机制研究;USP37促进肝细胞肝癌侵袭与转移的分子机制研究;USP37-MTA2/NuRD复合体促进肝细胞肝癌侵袭与转移的分子机制研究;北京市医院管理中心青苗计划

Role and clinical significance of MLLT1 super elongation complex subunit in the occurrence and development of hepatocellular carcinoma

YU  Hua-jing  WEI  Lu-yang  LIU  Shan-shan  GUAN  Cheng-jian  ZHANG  Zhong-tao*   

  1. Department of General Surgery, Beijing Friendship Hospital, Capital Medical University and National Clinical Research Center for Digestive Diseases, Beijing 100050, China
  • Received:2023-03-23 Revised:2023-04-19 Online:2023-08-06 Published:2023-08-06
  • Contact: ZHANG Zhong-tao E-mail:zhangzht@ccmu.edu.cn

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摘要：

目的  探讨MLLT1超伸长复合亚基（MLLT1）在肝细胞癌发生中的作用以及其对肝细胞癌免疫微环境的影响。   方法  利用多因素Cox回归分析以及GEPIA、UALCAN等肿瘤基因分析工具，探讨MLLT1基因在不同肿瘤中的表达情况和预后改变；利用Real-time PCR、免疫印迹、免疫组织化学方法探讨MLLT1在肝细胞癌肿瘤组织和正常组织间的表达差异；利用MTT实验、细胞周期实验检测敲低MLLT1对细胞增殖和细胞周期的影响；探讨MLLT1与肿瘤微环境中免疫细胞及免疫浸润的相关性，以及与免疫新抗原、免疫检查点、肿瘤突变负荷和微卫星不稳定性的相关性。   结果  MLLT1基因在包括肝细胞癌在内的多种实体瘤中异常表达，敲低MLLT1会抑制肝癌细胞增殖能力并对细胞周期造成阻滞，且MLLT1的高表达与肝细胞癌的不良预后相关。MLLT1的高表达也会影响肝细胞癌中CD4+T细胞、中性粒细胞等免疫细胞的浸润。   结论  MLLT1在肝细胞癌中高表达，MLLT1能够影响肝癌细胞增殖和破坏细胞周期，并通过影响免疫微环境的稳态在肝细胞癌发生发展中扮演重要角色。

关键词: MLLT1超伸长复合亚基, 肝细胞癌, 生物信息学, 免疫微环境, 预后分析, 实时定量聚合酶链反应, 免疫印迹法, 免疫组织化学

Abstract:

Objective  To investigate the role of MLLT1 in hepatocellular carcinoma （HCC）and its impact on the tumor immune microenvironment.    Methods  Multivariate Cox regression analysis and tumor gene analysis tools such as GEPIA and UALCAN were used to explore the expression of the MLLT1 gene and its prognostic significance in different tumors. Real-time PCR, Western blotting, and immunohistochemistry were used to investigate the differential expression of MLLT1 between HCC tumor tissue and normal tissue. MTT assay and cell cycle analysis were performed to assess the effect of MLLT1 knockdown on cell proliferation and cell cycle. The correlation between MLLT1 and immune cells, as well as immune infiltrates in the tumor microenvironment, and their correlation with immune neoantigens, immune checkpoints, tumor mutation burden, and microsatellite instability were also explored.    Results  The MLLT1 gene was found to be aberrantly expressed in various solid tumors including HCC, and its high expression was associated with poor prognosis in HCC. Knockdown of MLLT1 inhibited HCC cell proliferation and blocked the cell cycle. High expression of MLLT1 was found to affect the content of multiple immune cells, including CD4+T cells and neutrophile granulocyte cells in the HCC microenvironment.    Conclusion  MLLT1 is highly expressed in HCC and knockdown of MLLT1 can inhibit HCC cell proliferation and block the cell cycle. MLLT1 has a certain degree of impact on the immune microenvironment of HCC. Therefore, MLLT1 may serve as a potential diagnostic biomarker and therapeutic target for HCC.

Key words: MLLT1 super elongation complex subunit, Hepatocellular carcinoma, Bioinformatics, Immune microenvironment, Prognosis, Real-time PCR, Western blotting, Immunohistochemistry

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