Yu Jie, Cai Wenke, Zhou Tao, Men Bo, Chen Shunqiong, Tu Dong, Guo Wei, Wang Jicui, Zhao Feipeng, Wang Yan
Department of Thoracocardiac Surgery, 920th Hospital of Joint Logistics Support Force of Chinese People's Liberation Army, Kunming, Yunnan, China.
Department of Respiration, 920th Hospital of Joint Logistics Support Force of Chinese People's Liberation Army, Kunming, Yunnan, China.
Biochem Biophys Rep. 2024 Sep 26;40:101833. doi: 10.1016/j.bbrep.2024.101833. eCollection 2024 Dec.
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.
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.
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.
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.
肺癌导致显著的死亡率，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肺癌（NSCLC）的主要转移途径，并影响NSCLC的分期和预后。累积研究报道，癌胚抗原相关细胞粘附分子1（CEACAM1）参与多种癌症的进展。然而，很少有研究讨论CEACAM1在NSCLC淋巴管生成中的作用。在此，我们研究了CEACAM1如何影响NSCLC中的淋巴管生成。
前瞻性选择30例诊断为LN转移的原发性肺鳞状细胞癌（LUSC）患者。收集LUSC肿瘤组织、癌旁组织和阳性淋巴结组织。通过免疫组织化学检测临床样本中CEACAM1、CD31和LVYE1的表达及亚细胞定位。接下来，通过qPCR检测CEACAM1和hsa-miR-423-5p的表达。通过蛋白质印迹法检测HDLECs中淋巴管生成相关蛋白和NF-κB途径关键细胞因子的蛋白表达。进行管形成试验以检测不同组中的淋巴管生成。使用双荧光素酶试验验证CEACAM1与hsa-miR-423-5p之间的相互作用。
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。hsa-miR-423-5p过表达通过靶向CEACAM1抑制淋巴管生成。最后，我们观察到CEACAM1可激活NF-κB途径，从而促进淋巴管生成。
我们发现CEACAM1通过激活NF-κB增强NSCLC中的淋巴管生成，并被miR-423-5p抑制。这表明CEACAM1作为NSCLC新治疗标志物的价值。
