Long non-coding RNA (lncRNA) colon cancer-associated transcript-1 (CCAT1) has been reported to play important roles in the development and progression of multiple human malignancies. However, the functional role and molecular mechanism of CCAT1 on gefitinib resistance in non-small cell lung cancer (NSCLC) are largely unclear. The aim of this study is to explore the roles of CCAT1 on gefitinib resistance in NSCLC and to explore the underlying mechanisms. The quantitative real-time PCR (qRT-PCR) analysis was to investigate the expression pattern of CCAT1 in gefitinib-resistant NSCLC patient tissues and cell lines, and then the effects of CCAT1 on gefitinib resistance of NSCLC in vitro and in vivo. Furthermore, bioinformatics online program predictions and luciferase reporter assay were used to validate the association of CCAT1 and miR-218 in NSCLC cells. In this study, CCAT1 was observed to be upregulated in gefitinib-resistant patient tissues and cell lines. In vitro and in vivo experiments demonstrated that CCAT1 knockdown impaired cell proliferation and promoted the gefitinib-induced cell apoptosis. Furthermore, we demonstrated that CCAT1 acts as a sponge for miR-218, and verified that HOXA1 is a novel target of miR-218. These results suggest that CCAT1 may serve as a promising therapeutic target for the treatment of epidermal growth factor receptor (EGFR) plus NSCLC patients.

中文翻译：

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lncRNA CCAT1充当MicroRNA-218海绵，通过靶向HOXA1增加NSCLC中的吉非替尼耐药性。

据报道，长非编码RNA（lncRNA）结肠癌相关转录本1（CCAT1）在多种人类恶性肿瘤的发生和发展中起着重要作用。然而，CCAT1在非小细胞肺癌（NSCLC）中对吉非替尼耐药的功能作用和分子机制尚不清楚。本研究的目的是探讨CCAT1对非小细胞肺癌吉非替尼耐药的作用及其潜在机制。定量实时PCR（qRT-PCR）分析旨在研究耐吉非替尼的NSCLC患者组织和细胞系中CCAT1的表达模式，然后研究CCAT1对NSCLC吉非替尼耐药的体外和体内作用。此外，生物信息学在线程序预测和萤光素酶报告基因分析用于验证NSCLC细胞中CCAT1和miR-218的关联。在这项研究中，观察到CCAT1在耐吉非替尼的患者组织和细胞系中上调。体外和体内实验证明，CCAT1敲低会损害细胞增殖并促进吉非替尼诱导的细胞凋亡。此外，我们证明了CCAT1充当miR-218的海绵，并证实HOXA1是miR-218的新型靶标。这些结果表明，CCAT1可以作为表皮生长因子受体（EGFR）加NSCLC患者的有前途的治疗靶标。体外和体内实验表明，CCAT1敲低可损害细胞增殖并促进吉非替尼诱导的细胞凋亡。此外，我们证明了CCAT1充当miR-218的海绵，并证实HOXA1是miR-218的新型靶标。这些结果表明，CCAT1可以作为表皮生长因子受体（EGFR）和NSCLC患者的有前途的治疗靶标。体外和体内实验表明，CCAT1敲低可损害细胞增殖并促进吉非替尼诱导的细胞凋亡。此外，我们证明了CCAT1充当miR-218的海绵，并证实HOXA1是miR-218的新型靶标。这些结果表明，CCAT1可以作为表皮生长因子受体（EGFR）加NSCLC患者的有前途的治疗靶标。