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DPP4/CD26 表达对 SARS-CoV-2 易感性、免疫反应的影响,以及腺苷(衍生物 mA 和 CD)对癌症患者和健康个体的调节作用。

Effect of DPP4/CD26 expression on SARS‑CoV‑2 susceptibility, immune response, adenosine (derivatives mA and CD) regulations on patients with cancer and healthy individuals.

机构信息

Key Laboratory of Epigenetics and Oncology, The Research Center for Preclinical Medicine, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China.

Department of Biochemistry and Molecular Biology, School of Life Sciences, Central South University, Changsha, Hunan 410013, P.R. China.

出版信息

Int J Oncol. 2023 Mar;62(3). doi: 10.3892/ijo.2023.5489. Epub 2023 Feb 17.

Abstract

The worldwide COVID‑19 pandemic was brought on by a new coronavirus (SARS Cov‑2). A marker/receptor called Dipeptidyl peptidase 4/CD26(DPP4/CD26) may be crucial in determining susceptibility to tumors and coronaviruses. However, the regulation of DPP4 in COVID‑invaded cancer patients and its role on small molecule compounds remain unclear. The present study used the Human Protein Atlas, Monaco, and Schmiedel databases to analyze the expression of DPP4 in human tissues and immune cells. The association between DPP4 expression and survival in various tumor tissues was compared using GEPIA 2. The DNMIVD database was used to analyze the correlation between DPP4 expression and promoter methylation in various tumors. On the cBioPortal network, the frequency of DNA mutations in various cancers was analyzed. The correlation between DPP4 expression and immunomodulators was analyzed by TISIDB database. The inhibitory effects of cordycepin (CD), N6, N6‑dimethyladenosine (mA) and adenosine (AD) on DPP4 in cancer cells were evaluated. DPP4 was mainly expressed in endocrine tissue, followed by gastrointestinal tract, female tissue (mainly in placenta), male tissue (mainly in prostate and seminal vesicle), proximal digestive tract, kidney, bladder, liver, gallbladder and respiratory system. In immune cells, DPP4 mRNA was mainly expressed in T cells, and its expression was upregulated in esophageal carcinoma, kidney renal papillary cell carcinoma (KIRP), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma, pancreatic adenocarcinoma, prostate adenocarcinoma, stomach adenocarcinoma, thyroid carcinoma and thymoma. However, it was downregulated in breast invasive carcinoma, kidney chromophobe, lung squamous cell carcinoma and skin cutaneous melanoma. Thus, DPP4 is involved in viral invasion in most types of cancer. The expression of DPP4 could be inhibited by CD, mA and AD in different tumor cells. Moreover, CD significantly inhibited the formation of GFP‑positive syncytial cells. experiments with AD injection further showed that AD significantly inhibited lymphocyte activating factor 3 expression. These drugs may have potential to treat COVID‑19 by targeting DPP4. Thus, DPP4 may be medically significant for SARS‑CoV‑2‑infected cancer patients, providing prospective novel targets and concepts for the creation of drugs against COVID‑19.

摘要

新型冠状病毒(SARS-CoV-2)引发了全球 COVID-19 大流行。二肽基肽酶 4/CD26(DPP4/CD26)等标志物/受体可能对肿瘤和冠状病毒易感性至关重要。然而,COVID-19 入侵癌症患者的 DPP4 调节及其在小分子化合物中的作用尚不清楚。本研究使用人类蛋白质图谱、摩纳哥和施密德尔数据库分析了 DPP4 在人组织和免疫细胞中的表达。使用 GEPIA2 比较了 DPP4 表达与各种肿瘤组织中生存的相关性。使用 DNMIVD 数据库分析了各种肿瘤中 DPP4 表达与启动子甲基化的相关性。在 cBioPortal 网络上,分析了各种癌症中 DNA 突变的频率。通过 TISIDB 数据库分析了 DPP4 表达与免疫调节剂的相关性。评估了虫草素(CD)、N6、N6-二甲基腺苷(mA)和腺苷(AD)对癌细胞中 DPP4 的抑制作用。DPP4 主要在内分泌组织中表达,其次是胃肠道、女性组织(主要在胎盘)、男性组织(主要在前列腺和精囊)、近端消化道、肾脏、膀胱、肝脏、胆囊和呼吸系统。在免疫细胞中,DPP4mRNA 主要在 T 细胞中表达,其在食管癌、肾肾乳头细胞癌(KIRP)、肝肝癌(LIHC)、肺腺癌、胰腺腺癌、前列腺腺癌、胃腺癌、甲状腺癌和胸腺瘤中表达上调。然而,在乳腺癌浸润性癌、肾嫌色细胞癌、肺鳞状细胞癌和皮肤黑色素瘤中表达下调。因此,DPP4 参与了大多数类型癌症中的病毒入侵。CD、mA 和 AD 可抑制不同肿瘤细胞中 DPP4 的表达。此外,CD 可显著抑制 GFP 阳性合胞体的形成。用 AD 注射进行的实验进一步表明,AD 可显著抑制淋巴细胞激活因子 3 的表达。这些药物可能通过靶向 DPP4 具有治疗 COVID-19 的潜力。因此,DPP4 对 SARS-CoV-2 感染的癌症患者可能具有重要的医学意义,为 COVID-19 药物的研发提供了有前景的新靶点和概念。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edc2/9946808/13a2205f9a25/IJO-62-3-05489-g00.jpg

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