African American (AA) populations present with notably higher incidence and mortality rates from lung cancer in comparison to other racial groups. Here, we elucidated the contribution of long non-coding RNAs (lncRNAs) in the racial disparities and their potential clinical applications in both diagnosis and therapeutic strategies. AA patients had elevated plasma levels of MALAT1 and PVT1 compared with cancer-free smokers. Incorporating these lncRNAs as plasma biomarkers, along with smoking history, achieved 81% accuracy in diagnosis of lung cancer in AA patients. We observed a rise in MALAT1 expression, correlating with increased levels of monocyte chemoattractant protein-1 (MCP-1) and CD68, CD163, CD206, indicative of tumor-associated macrophages in lung tumors of AA patients. Forced MALAT1 expression led to enhanced growth and invasiveness of lung cancer cells, both in vitro and in vivo, accompanied by elevated levels of MCP-1, CD68, CD163, CD206, and KI67. Mechanistically, MALAT1 acted as a competing endogenous RNA to directly interact with miR-206, subsequently affecting MCP-1 expression and macrophage activity, and enhanced the tumorigenesis. Targeting MALAT1 significantly reduced tumor sizes in animal models. Therefore, dysregulated MALAT1 contributes to lung cancer disparities in AAs by modulating the tumor immune microenvironment through its interaction with miR-206, thereby presenting novel diagnostic and therapeutic targets.
与其他种族群体相比，非洲裔美国人（AA）的肺癌发病率和死亡率显著更高。本研究阐明了长链非编码RNA（lncRNAs）在种族差异中的作用及其在诊断和治疗策略中的潜在临床应用。与非吸烟癌症患者相比，AA患者的血浆中MALAT1和PVT1水平升高。将这些lncRNAs作为血浆生物标志物，结合吸烟史，对AA患者肺癌的诊断准确率达到81%。我们观察到MALAT1表达升高，与单核细胞趋化蛋白-1（MCP-1）以及CD68、CD163、CD206水平升高相关，表明AA患者肺肿瘤中存在肿瘤相关巨噬细胞。强制表达MALAT1导致肺癌细胞在体外和体内的生长和侵袭能力增强，同时伴随MCP-1、CD68、CD163、CD206和KI67水平升高。机制上，MALAT1作为竞争性内源RNA直接与miR-206相互作用，进而影响MCP-1表达和巨噬细胞活性，并增强肿瘤发生。靶向MALAT1在动物模型中显著减小了肿瘤体积。因此，失调的MALAT1通过其与miR-206的相互作用调节肿瘤免疫微环境，从而导致了AA人群的肺癌差异，为诊断和治疗提供了新的靶点。
肿瘤(癌症)患者之家