Exosomes could mediate cell-cell crosstalk in cancer progression by transferring long noncoding RNAs (lncRNAs). The aim of this study is to explore the roles of the exosomal lncRNA urothelial carcinoma-associated 1 (UCA1) on gefitinib resistance in non-small cell lung cancer (NSCLC). First, we detected the expression of UCA1 in gefitinib-resistant and gefitinib-sensitive NSCLC by quantitative real-time PCR; the expression occurred in tissues, cell lines, and exosomes. Cell phenotypes and animal experiments were performed to determine the effects of UCA1 and exosomal UCA1. Furthermore, bioinformatics online programs and luciferase reporter assay were used to validate the association of UCA1 and miR-143 in NSCLC cells. We observed that UCA1 was increased in both gefitinib-resistant NSCLC cells and their secreted exosomes. In vitro and in vivo experiments demonstrated that UCA1 knockdown impaired cell proliferation and promoted the gefitinib-induced cell apoptosis. Then we demonstrated that repressed UCA1 promoted the miR-143 expression, and miR-143 could bind to the predicted binding site of UCA1. We then dissected the effect of miR-143 on gefitinib resistance in NSCLC and proved the suppressive role of miR-143. Furthermore, we found that miR-143 displayed its role via modulating the FOSL2 expression. In summary, our findings indicate that exosomal UCA1 may serve as a promising therapeutic target for the treatment of epidermal growth factor receptor-positive (EGFR⁺) NSCLC patients.

外来体可以通过转移长的非编码RNA（lncRNA）来介导癌症进程中的细胞间串扰。这项研究的目的是探索非小细胞肺癌（NSCLC）中外泌体lncRNA尿路上皮癌相关1（UCA1）对吉非替尼耐药的作用。首先，我们通过实时定量PCR检测了UCA1在耐吉非替尼和对吉非替尼敏感的NSCLC中的表达；该表达发生在组织，细胞系和外泌体中。进行细胞表型和动物实验以确定UCA1和外泌体UCA1的作用。此外，使用生物信息学在线程序和荧光素酶报告基因测定法验证了NSCLC细胞中UCA1和miR-143的关联。我们观察到，在对吉非替尼耐药的NSCLC细胞及其分泌的外泌体中，UCA1均增加。体外和体内实验表明，UCA1敲低会损害细胞增殖并促进吉非替尼诱导的细胞凋亡。然后，我们证明了抑制的UCA1促进了miR-143的表达，而miR-143可以与UCA1的预测结合位点结合。然后，我们剖析了miR-143对吉非替尼耐药的非小细胞肺癌的作用，并证明了miR-143的抑制作用。此外，我们发现miR-143通过调节FOSL2表达来显示其作用。总而言之，我们的发现表明外泌体UCA1可以作为表皮生长因子受体阳性（EGFR ⁺）NSCLC患者的有希望的治疗靶标。