TFAP2C-Activated MALAT1 Modulates the Chemoresistance of Docetaxel-Resistant Lung Adenocarcinoma Cells
TFAP2C-Activated MALAT1 Modulates the Chemoresistance of Docetaxel-Resistant Lung Adenocarcinoma Cells
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TFAP2C 激活的 MALAT1 调节多西他赛耐药肺腺癌细胞的化疗耐药性
DOI：
10.1016/j.omtn.2019.01.005
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发表时间：
2019-03-01
期刊：
影响因子：
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通讯作者：
Chen, Longbang
中科院分区：
文献类型：
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作者：
Chen, Jing;Liu, Xiaobei;Chen, Longbang
化疗耐药性是肺腺癌有效治疗的一大障碍。之前，我们验证了microRNA-200 b（miR-200 b）在多西他赛（DTX）耐药LUAD细胞形成中的作用。本研究旨在探讨MTX耐药的LUAD细胞中miR-200 b低水平表达的机制。应用实时逆转录（RT 2）lncRNA PCR阵列系统来探索可能在DTX抗性LUAD细胞中调控miR-200 b的lncRNA。转移相关肺腺癌转录本1（MALAT 1）导致MTX耐药LUAD细胞中miR-200 b水平较低。进行功能测定以确定MALAT 1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。MALAT 1通过作为ceRNA调节miR-200 b。MALAT 1可调节LUAD细胞对DTX的敏感性。E2 F转录因子3（E2 F3）和锌指E盒结合同源框1（ZEB 1）是miR-200 b的两个靶点，并介导MALAT 1在MTX耐药LUAD细胞中的功能。转录因子AP-2 γ（TFAP 2C）和ZEB 1激活MALAT 1转录。总之，TFAP 2C激活的MALAT 1通过海绵状miR-200 b上调E2 F3和ZEB 1来调节LUAD细胞的化学抗性。我们的研究结果可能为LUAD的治疗提供新的治疗靶点和前景。
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.