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含 MARVEL 跨膜结构域的趋化素样因子样 6:生物信息学与体外实验分析其在多形性胶质母细胞瘤中的作用

英文原题:Chemokine-like factor-like MARVEL transmembrane domain containing 6: Bioinformatics and experiments in vitro analyze in glioblastoma multiforme.

PubMed 2023/01/09(内容时间) Front Mol Neurosci Q2 · IF 4.4(JCR 2025)

研究概要

本文通过生物信息学分析和体外实验,对CMTM6在GBM中的作用进行了详细分析和验证,证明CMTM6可能是胶质瘤治疗的潜在靶点。

研究思路结论见上方概要

趋化素样因子(CKLF)样MARVEL跨膜结构域包含6(CMTM6)是一种定位于细胞膜的蛋白质,已知能够与PD-L1在质膜上共定位,防止PD-L1降解,并维持PD-L1在细胞膜上的表达。CMTM6在口腔鳞状细胞癌(OSCC)和结直肠癌(CRC)等多种肿瘤中高表达并发挥重要作用,然而其在多形性胶质母细胞瘤(GBM)中的作用尚不清楚。

本文为探究CMTM6在GBM中的作用,通过生物信息学分析了CMTM6在GBM中的表达、CMTM6与相关基因的相互作用。重要的是,我们分析了CMTM6在GBM中的表达与TIL(肿瘤浸润淋巴细胞)(TILs)、免疫抑制剂、免疫刺激剂、趋化因子和趋化因子受体的关系。我们进一步分析了CMTM6的功能,并通过体外实验进行验证。最后,还分析了CMTM6对药物的敏感性,并在体外验证了CMTM6与抗癌药物荜茇酰胺(PL)的关系。

结果显示,CMTM6在GBM中高表达,并与多个基因相关。此外,CMTM6与GBM中的免疫微环境和炎症反应密切相关。对CMTM6与GBM功能的生物信息学分析显示,我们的实验证明CMTM6显著促进了GBM细胞的迁移和上皮-间质转化(EMT),但对其他功能没有显著影响。有趣的是,我们发现在GBM中,PL促进CMTM6的表达。

展开英文摘要原文

INTRODUCTION: Chemokine-like factor (CKLF)-like MARVEL transmembrane domain containing 6 (CMTM6) is a protein localized to the cell membrane and is known for its ability to co-localize with PD-L1 on the plasma membrane, prevent PD-L1 degradation, and maintain PD-L1 expression on the cell membrane. CMTM6 is highly expressed and plays an important role in various tumors such as oral squamous cell carcinoma (OSCC) and colorectal cancer (CRC), however, its role in Glioblastoma multiforme (GBM) is unclear. METHODS: In this paper, to investigate the role of CMTM6 in GBM, we analyzed the expression of CMTM6 in GBM, the interaction with CMTM6 and the associated genes by bioinformatics. Importantly, we analyzed the expression of CMTM6 in GBM in relation to tumor-infiltrating lymphocytes (TILs), immunoinhibitors, immunostimulators, chemokines and chemokine receptors. We further analyzed the function of CMTM6 and performed in vitro experiments to verify it. Finally, the sensitivity of CMTM6 to drugs was also analyzed and the relationship between CMTM6 and the anticancer drug Piperlonguminine (PL) was verified in vitro . RESULTS: The results showed that CMTM6 was highly expressed in GBM and correlated with multiple genes. Furthermore, CMTM6 is closely related to the immune microenvironment and inflammatory response in GBM. Bioinformatic analysis of CMTM6 correlated with the function of GBM, and our experiments demonstrated that CMTM6 significantly promoted the migration of GBM cells and epithelial-mesenchymal transition (EMT), but had no significant effect on other functions. Interestingly, we found that in GBM, PL promotes the expression of CMTM6. DISCUSSION: In this paper, we have performed a detailed analysis and validation of the role of CMTM6 in GBM using bioinformatics analysis and in vitro experiments to demonstrate that CMTM6 may be a potential target for glioma therapy.

论文信息

作者
Meng H、Li S、Li Q、Wang Y、Wang G、Qu Y
第一作者单位
Department of Emergency Medicine, Medical College of Qingdao University, Qingdao, Shandong, China.China
通讯作者单位
Department of Intensive Care Unit, Affiliated Qingdao Municipal Hospital of Qingdao University, Qingdao, Shandong, China.China
期刊
Frontiers in molecular neuroscience2022
原文标识
PubMed 36698778 · DOI 10.3389/fnmol.2022.1026927