Abstract：
Transmembrane proteins play key roles in the development of lung cancer. The family with sequence similarity 189 member A2 (FAM189A2) gene encodes a transmembrane structural protein, yet its involvement in lung adenocarcinoma remains largely unexplored. This study elucidated its role in lung adenocarcinoma and its possible molecular mechanism. Our findings revealed diminished expression levels of FAM189A2 in LUAD tissues. Additionally, the activity of LUAD cells was significantly inhibited by overexpression of FAM189A2. Following FAM189A2 overexpression, the expression of OCLN and TJP2 was upregulated in LUAD cells, while CXCR4 expression experiences a notable decrease. Moreover, the coimmunoprecipitation experiment confirmed the direct interaction between FAM189A2 and CXCR4. The infiltration levels of T cells (CD4+ memory resting, CD8+, regulatory), NK cells, B memory cells, endothelial cells and cancer-associated fibroblasts were significantly correlated with FAM189A2 expression. These results indicate FAM189A2 may act as a tumour suppressor in LUAD through tight junction protein (TJP) and CXCR4 regulation. Moreover, FAM189A2 is significantly correlated with the immune microenvironment of LUAD, which may be involved in prognosis and immunotherapeutic efficacy.
摘要：
跨膜蛋白在肺癌的发生发展中起关键作用。具有序列相似性的家族189成员A2(FAM189A2)基因编码跨膜结构蛋白,然而，其在肺腺癌中的参与仍未被研究。本研究阐明了其在肺腺癌中的作用及其可能的分子机制。我们的发现揭示了LUAD组织中FAM189A2的表达水平降低。此外,过表达FAM189A2可显著抑制LUAD细胞的活性。FAM189A2过表达后，LUAD细胞中OCLN和TJP2的表达上调,而CXCR4表达经历显著下降。此外，免疫共沉淀实验证实了FAM189A2和CXCR4之间的直接相互作用。T细胞浸润水平（CD4+记忆静息，CD8+,监管)，NK细胞,B记忆单元,内皮细胞和癌相关成纤维细胞与FAM189A2表达显著相关.这些结果表明FAM189A2可能通过紧密连接蛋白（TJP）和CXCR4调节在LUAD中充当肿瘤抑制因子。此外，FAM189A2与LUAD的免疫微环境显著相关,这可能与预后和免疫治疗效果有关。
