Chemoresistance remains a great obstacle in effective lung adenocarcinoma (LUAD) treatment. Previously, we verified the role of microRNA-200b (miR-200b) in the formation of docetaxel (DTX)-resistant LUAD cells. This study aims to investigate the mechanism underlying the low level of miR-200b in DTX-resistant LUAD cells. The real-time reverse transcription (RT²) lncRNA PCR array system was applied to explore lncRNAs that potentially regulated miR-200b in DTX-resistant LUAD cells. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) contributed to the low miR-200b level in DTX-resistant LUAD cells. Functional assays were conducted to determine the role of MALAT1 in regulating the growth and metastasis of parental and DTX-resistant LUAD cells. Investigation revealed the mechanism of the competing endogenous RNA (ceRNA) pathway. MALAT1 regulated miR-200b by acting as a ceRNA. MALAT1 modulated the sensitivity of LUAD cells to DTX. E2F transcription factor 3 (E2F3) and zinc-finger E-box binding homeobox 1 (ZEB1) were two targets of miR-200b and mediated the function of MALAT1 in DTX-resistant LUAD cells. Transcription factor AP-2 gamma (TFAP2C) and ZEB1 activated the MALAT1 transcription. In conclusion, TFAP2C-activated MALAT1 modulated the chemoresistance of LUAD cells by sponging miR-200b to upregulate E2F3 and ZEB1. Our findings may provide novel therapeutic targets and perspectives for LUAD treatment.

化疗耐药仍然是有效治疗肺腺癌（LUAD）的一大障碍。此前，我们验证了 microRNA-200b (miR-200b) 在多西他赛 (DTX) 耐药 LUAD 细胞形成中的作用。本研究旨在探讨 DTX 耐药 LUAD 细胞中 miR-200b 低水平的机制。应用实时逆转录 (RT ² ) lncRNA PCR 阵列系统来探索 DTX 耐药 LUAD 细胞中可能调节 miR-200b 的 lncRNA。转移相关肺腺癌转录物 1 (MALAT1) 导致 DTX 耐药 LUAD 细胞中 miR-200b 水平较低。进行功能测定以确定 MALAT1 在调节亲本和 DTX 抗性 LUAD 细胞的生长和转移中的作用。研究揭示了竞争性内源 RNA (ceRNA) 途径的机制。 MALAT1 通过充当 ceRNA 来调节 miR-200b。 MALAT1 调节 LUAD 细胞对 DTX 的敏感性。 E2F 转录因子 3 (E2F3) 和锌指 E 盒结合同源盒 1 (ZEB1) 是 miR-200b 的两个靶标，在 DTX 抗性 LUAD 细胞中介导 MALAT1 的功能。转录因子 AP-2 gamma (TFAP2C) 和 ZEB1 激活 MALAT1 转录。总之，TFAP2C 激活的 MALAT1 通过海绵 miR-200b 上调 E2F3 和 ZEB1 来调节 LUAD 细胞的化疗耐药性。我们的研究结果可能为 LUAD 治疗提供新的治疗靶点和前景。