EMG1 在肺腺癌进展中的作用：对预后和免疫细胞浸润的影响。

The role of EMG1 in lung adenocarcinoma progression: Implications for prognosis and immune cell infiltration.

机构信息

Anhui Province Key Laboratory of Non-coding RNA Basic and Clinical Transformation (Wannan Medical College), Wuhu 241001, Anhui, China; Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution (Wannan Medical College), Wuhu 241001, Anhui, China; Central Laboratory, Yijishan Hospital, The First Affiliated Hospital of Wannan Medical College, Wuhu 241001, Anhui, China; Non-coding RNA Research Center of Wannan Medical College, Wuhu, Anhui 241001, China; Clinical Research Center for Critical Respiratory Medicine of Anhui Province, Yijishan Hospital, The First Affiliated Hospital of Wannan Medical College, Wuhu 241001, Anhui, China.

Anhui Province Key Laboratory of Non-coding RNA Basic and Clinical Transformation (Wannan Medical College), Wuhu 241001, Anhui, China; Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution (Wannan Medical College), Wuhu 241001, Anhui, China; Clinical Research Center for Critical Respiratory Medicine of Anhui Province, Yijishan Hospital, The First Affiliated Hospital of Wannan Medical College, Wuhu 241001, Anhui, China; Department of Nuclear Medicine, Yijishan Hospital, The First Affiliated Hospital of Wannan Medical College, Wuhu, Anhui 241001, China.

出版信息

Int Immunopharmacol. 2024 Sep 10;138:112553. doi: 10.1016/j.intimp.2024.112553. Epub 2024 Jun 28.

DOI:10.1016/j.intimp.2024.112553

PMID:38943975

Abstract

BACKGROUND AND AIMS

Lung adenocarcinoma (LUAD) is the most common and aggressive cancer with a high incidence. N1-specific pseudouridine methyltransferase (EMG1), a highly conserved nucleolus protein, plays an important role in the biological development of ribosomes. However, the role of EMG1 in the progression of LUAD is still unclear.

METHODS

The expression of EMG1 in LUAD cells, and LUAD tissues, and adjacent noncancerous tissues was quantified using real-time polymerase chain reaction (PCR) and western blotting. The roles of EMG1 in LUAD cell proliferation, migration, invasion and tumorigenicity were explored in vitro and in vivo. Western blot analysis to underlying molecular mechanism of EMG1 regulating the biological function of LUAD. EMG1 expression and its impact on tumor prognosis were analyzed using a range of databases including GEPIA, UALCAN, cBioPortal, LinkedOmics, and Kaplan-Meier Plotter.

RESULTS

EMG1 expression was elevated in LUAD patients compared to normal tissues, and EMG1 expression was strongly correlated with prognosis in LUAD patients. EMG1 expression correlated with age, gender, N stage, T stage, and pathologic stage. EMG1 expression was strongly positively correlated with MRPL51, PHB2, SNRPG, ATP5MD, and TPI1, and strongly negatively correlated with MACF1, DOCK9, RAPGEF2, SYNJ1, and KIDINS220, the major enrichment pathways for EMG1 and related genes include Cell cycle, DNA Replication and Pathways in cancer signaling pathways. EMG1 expression level was significantly increased in LUAD cell lines and tissues. Knockdown of EMG1 could inhibit LUAD cell proliferation, migration, invasion, and tumorigenicity. Besides, EMG1 overexpression could promote LUAD cell proliferation, migration, and invasion. High expression of EMG1 predicts poor prognosis in LUAD patients, and EMG1 may play an oncogenic role in the tumor microenvironment by participating in the infiltration of LUAD immune cells.

CONCLUSIONS

EMG1 regulated various functions in LUAD by directly mediating Akt/mTOR/p70s6k signaling pathways activation. The results suggest that EMG1 may be a novel biomarker for assessing prognosis and immune cell infiltration in LUAD.

摘要

背景与目的

肺腺癌（LUAD）是最常见且侵袭性最强的癌症之一，发病率较高。N1 特异性假尿嘧啶甲基转移酶（EMG1）是一种高度保守的核仁蛋白，在核糖体的生物发育中发挥着重要作用。然而，EMG1 在 LUAD 进展中的作用尚不清楚。

方法

采用实时聚合酶链反应（PCR）和 Western blot 定量检测 LUAD 细胞和组织以及相邻非癌组织中 EMG1 的表达。在体外和体内研究 EMG1 对 LUAD 细胞增殖、迁移、侵袭和致瘤性的作用。Western blot 分析揭示了 EMG1 调节 LUAD 生物学功能的潜在分子机制。利用 GEPIA、UALCAN、cBioPortal、LinkedOmics 和 Kaplan-Meier Plotter 等多种数据库分析 EMG1 表达及其对肿瘤预后的影响。

结果

与正常组织相比，LUAD 患者的 EMG1 表达升高，并且 EMG1 表达与 LUAD 患者的预后密切相关。EMG1 表达与年龄、性别、N 分期、T 分期和病理分期相关。EMG1 表达与 MRPL51、PHB2、SNRPG、ATP5MD 和 TPI1 呈强正相关，与 MACF1、DOCK9、RAPGEF2、SYNJ1 和 KIDINS220 呈强负相关，EMG1 及其相关基因的主要富集途径包括细胞周期、DNA 复制和癌症信号通路。EMG1 表达水平在 LUAD 细胞系和组织中显著升高。敲低 EMG1 可抑制 LUAD 细胞增殖、迁移、侵袭和致瘤性。此外，过表达 EMG1 可促进 LUAD 细胞增殖、迁移和侵袭。EMG1 高表达预示 LUAD 患者预后不良，EMG1 可能通过参与 LUAD 免疫细胞浸润在肿瘤微环境中发挥致癌作用。