CEACAM1 通过 miR-423-5p 和 NF- kB 增加非小细胞肺癌的淋巴管生成

IF 2.3 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry and Biophysics Reports Pub Date : 2024-09-26 DOI:10.1016/j.bbrep.2024.101833

Jie Yu , Wenke Cai , Tao Zhou , Bo Men , Shunqiong Chen , Dong Tu , Wei Guo , Jicui Wang , Feipeng Zhao , Yan Wang

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引用次数: 0

摘要

背景肺癌会导致大量死亡，侵袭和转移是导致大多数癌症死亡的主要特征。淋巴结转移是非小细胞癌（NSCLC）的主要转移途径，影响着 NSCLC 的分期和预后。大量研究表明，癌胚抗原相关细胞粘附分子 1（CEACAM1）参与了多种癌症的进展。然而，很少有研究讨论 CEACAM1 在 NSCLC 淋巴管生成中的功能。本文研究了 CEACAM1 如何影响 NSCLC 的淋巴管生成。方法前瞻性地选择了 30 例确诊为 LN 转移的原发性鳞状细胞癌（LUSC）患者。方法前瞻性地选择了30例确诊为淋巴结转移的原发性鳞状细胞癌（LUSC）患者，采集了LUSC肿瘤组织、癌旁组织和阳性淋巴结组织。通过免疫组化检测临床样本中 CEACAM1、CD31 和 LVYE1 的表达和亚细胞位置。然后，通过 qPCR 检测 CEACAM1 和 hsa-miR-423-5p 的表达。通过 Western 印迹检测了 HDLECs 中淋巴管生成相关蛋白和 NF-κB 通路关键细胞因子的蛋白表达。用试管形成试验检测不同组淋巴管生成的情况。结果发现 CEACAM1 是与肺癌预后相关的潜在基因。它与血管生成和淋巴管生成呈正相关。然后，我们检测了 CEACAM1 在淋巴管生成中的功能，发现 CEACAM1 促进淋巴管生成。最后，我们观察到 CEACAM1 可激活 NF-κB 通路，从而促进淋巴管生成。这表明 CEACAM1 可作为一种新的 NSCLC 治疗标记物。

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CEACAM1 increased the lymphangiogenesis through miR-423-5p and NF- kB in Non-Small Cell Lung Cancer

Background

Lung cancer causes significant mortality, with invasion and metastasis being the main features that cause most cancer deaths. Lymph node metastasis is the primary metastatic route in non-small cell carcinoma (NSCLC) and influences the staging and prognosis of NSCLC. Cumulative studies have reported that Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is involved in the progression of various cancers. However, few studies have discussed the function of CEACAM1 in lymphangiogenesis in NSCLC. Here, we examined how CEACAM1 influences lymphangiogenesis in NSCLC.

Methods

A total of 30 primary squamous cell carcinoma (LUSC) patients diagnosed with LN metastasis were prospectively selected. LUSC tumor tissues, para-cancerous tissues, and positive lymph node tissues were harvested. The expression and subcellular location of CEACAM1, CD31, and LVYE1 in clinical samples were detected by immunohistochemistry. Next, the CEACAM1 and hsa-miR-423-5p expressions were detected by qPCR. The protein expression of lymphangiogenesis-associated proteins and critical cytokines of the NF–κB pathway in HDLECs was detected by Western blot. A tube formation assay was performed to detect the lymphangiogenesis in different groups. The interaction between CEACAM1 and hsa-miR-423-5p was verified using a dual luciferase assay.

Results

CEACAM1 was found to be a potential gene associated with lung cancer prognosis. It was positively correlated with angiogenesis and lymphangiogenesis. Then, we detected the function of CEACAM1 in lymphangiogenesis and found that CEACAM1 promoted lymphangiogenesis. hsa-miR-423-5p overexpression inhibited lymphangiogenesis via targeting CEACAM1. Finally, we observed that CEACAM1 can activate the NF–κB pathway and, therefore, promote lymphangiogenesis.

Conclusion

We found that CEACAM1 enhanced lymphangiogenesis in NSCLC via NF-kB activation and was repressed by miR-423-5p. This suggests the value of CEACAM1 as a new therapeutic marker in NSCLC.

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来源期刊

Biochemistry and Biophysics Reports Biochemistry, Genetics and Molecular Biology-Biophysics

CiteScore

4.60

自引率

0.00%

发文量

191

审稿时长

59 days

期刊介绍： Open access, online only, peer-reviewed international journal in the Life Sciences, established in 2014 Biochemistry and Biophysics Reports (BB Reports) publishes original research in all aspects of Biochemistry, Biophysics and related areas like Molecular and Cell Biology. BB Reports welcomes solid though more preliminary, descriptive and small scale results if they have the potential to stimulate and/or contribute to future research, leading to new insights or hypothesis. Primary criteria for acceptance is that the work is original, scientifically and technically sound and provides valuable knowledge to life sciences research. We strongly believe all results deserve to be published and documented for the advancement of science. BB Reports specifically appreciates receiving reports on: Negative results, Replication studies, Reanalysis of previous datasets.