Metastasis, a major cause of cancer-related mortality worldwide, frequently occurs early in the diagnosis of lung adenocarcinoma (LUAD). However, the precise molecular mechanisms governing the aggressive metastatic behavior of LUAD remain incompletely understood. In this study, we present compelling evidence indicating that the long noncoding RNA linc01703 is significantly downregulated in metastatic lung cancer cells. Intriguingly, in vivo experiments revealed that Linc01703 exerted a profound inhibitory effect on lung cancer metastasis without discernible impact on the in vitro proliferation or invasion capacities of LUAD cells. Mechanistically, Linc01703 enhanced the interaction between Rab27a, SYTL1, and CD81, consequently promoting the secretion of CD81+exosomes. These exosomes, in turn, suppressed the infiltration of immune cells within the tumor microenvironment, thereby impeding LUAD metastasis. Importantly, our analysis of lung cancer tissues revealed a correlation between reduced CD81 expression and an unfavorable patient prognosis. Collectively, our findings suggest that Linc01703 functions as a metastasis suppressor by facilitating the secretion of CD81+exosomes through the formation of the Rab27a/SYTL1/CD81 complex.
转移是全球癌症相关死亡的主要原因，在肺腺癌诊断时常早期发生。然而，调控肺腺癌侵袭性转移行为的确切分子机制尚未完全阐明。本研究提供了有力证据，表明长链非编码RNA linc01703在转移性肺癌细胞中显著下调。值得注意的是，体内实验显示Linc01703对肺癌转移具有显著抑制作用，但对肺腺癌细胞的体外增殖或侵袭能力未见明显影响。机制研究表明，Linc01703通过增强Rab27a、SYTL1与CD81之间的相互作用，进而促进CD81+外泌体的分泌。这些外泌体能够抑制肿瘤微环境中免疫细胞的浸润，从而阻碍肺腺癌转移。重要的是，我们对肺癌组织的分析显示CD81表达降低与患者不良预后相关。综上所述，我们的研究结果表明Linc01703通过形成Rab27a/SYTL1/CD81复合体促进CD81+外泌体分泌，从而发挥转移抑制因子的功能。
肿瘤(癌症)患者之家