Cisplatin resistance has been long considered an obstacle to the efficacy of chemotherapy in non-small-cell lung cancer (NSCLC). Long non-coding RNAs (lncRNAs) have been widely reported to participate in the various biological process including cancer. In the present study, we aim to explore the functions of Linc00221 and miR-519a in the sensitivity and the resistance of NSCLC to cisplatin. The levels of Linc00221, miR-519a, and zinc finger and BTB domain-containing five (ZBTB5) in NSCLC tissues were detected by qRT-PCR and Western blot. Colony formation and MTT assays were applied to detect the viability of cells after cisplatin treatment. Dual luciferase reporter assays were used to detect the inhibitory effect of miR-519a on ZBTB5 and Linc00221, and pull down experiments were employed to determine the direct interaction between Linc00221 and miR-519a. Our results showed that Linc00221 was highly expressed in cisplatin-resistant NSCLC tissues and cells and closely associated with poor prognosis. Linc00221 promoted the cisplatin resistance of NSCLC and miR-519a was a direct target of Linc00221. In addition, miR-519a could promote cisplatin sensitivity in NSCLC cells by targeting ZBTB5. Linc00221 could mediate the cisplatin sensitivity in NSCLC by adsorbing miR-519a to prevent its down-regulation of ZBTB5. In conclusion, Linc00221 promotes cisplatin resistance in NSCLC through the downstream miR-519a/ZBTB5 signaling axis, which could be used as a potential diagnostic and therapeutic target for clinical cisplatin-resistant NSCLC patients.

中文翻译：

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Linc00221通过海绵miR-519a调节非小细胞肺癌中的顺铂耐药性。

长期以来，顺铂耐药性一直被认为是非小细胞肺癌（NSCLC）化疗疗效的障碍。长的非编码RNA（lncRNA）已被广泛报道参与包括癌症在内的各种生物过程。在本研究中，我们旨在探讨Linc00221和miR-519a在NSCLC对顺铂的敏感性和耐药性中的功能。通过qRT-PCR和Western blot检测NSCLC组织中Linc00221，miR-519a以及锌指和含BTB结构域的五个（ZBTB5）的水平。集落形成和MTT测定法用于检测顺铂处理后细胞的活力。使用双重萤光素酶报告基因检测法检测miR-519a对ZBTB5和Linc00221的抑制作用，并进行下拉实验来确定Linc00221与miR-519a之间的直接相互作用。我们的结果表明，Linc00221在耐顺铂的NSCLC组织和细胞中高表达，并与不良预后密切相关。Linc00221促进了NSCLC的顺铂耐药性，而miR-519a是Linc00221的直接靶标。另外，miR-519a可以通过靶向ZBTB5来促进NSCLC细胞中的顺铂敏感性。Linc00221可以通过吸附miR-519a来阻止其对ZBTB5的下调，从而介导NSCLC的顺铂敏感性。总之，Linc00221通过下游miR-519a / ZBTB5信号传导轴促进NSCLC的顺铂耐药性，可用作临床对顺铂耐药的NSCLC患者的潜在诊断和治疗靶标。我们的结果表明，Linc00221在耐顺铂的NSCLC组织和细胞中高表达，并与不良预后密切相关。Linc00221促进了NSCLC的顺铂耐药性，而miR-519a是Linc00221的直接靶标。另外，miR-519a可以通过靶向ZBTB5来促进NSCLC细胞中的顺铂敏感性。Linc00221可以通过吸附miR-519a来阻止其对ZBTB5的下调，从而介导NSCLC的顺铂敏感性。总之，Linc00221通过下游miR-519a / ZBTB5信号传导轴促进NSCLC的顺铂耐药性，可用作临床对顺铂耐药的NSCLC患者的潜在诊断和治疗靶标。我们的结果表明，Linc00221在耐顺铂的NSCLC组织和细胞中高表达，并与不良预后密切相关。Linc00221促进了NSCLC的顺铂耐药性，而miR-519a是Linc00221的直接靶标。另外，miR-519a可以通过靶向ZBTB5来促进NSCLC细胞中的顺铂敏感性。Linc00221可以通过吸附miR-519a来阻止其对ZBTB5的下调，从而介导NSCLC的顺铂敏感性。总之，Linc00221通过下游miR-519a / ZBTB5信号转导轴促进NSCLC的顺铂耐药性，可用作临床对顺铂耐药的NSCLC患者的潜在诊断和治疗靶标。Linc00221促进了NSCLC的顺铂耐药性，而miR-519a是Linc00221的直接靶标。另外，miR-519a可以通过靶向ZBTB5来促进NSCLC细胞中的顺铂敏感性。Linc00221可以通过吸附miR-519a来阻止其对ZBTB5的下调，从而介导NSCLC的顺铂敏感性。总之，Linc00221通过下游miR-519a / ZBTB5信号转导轴促进NSCLC的顺铂耐药性，可用作临床对顺铂耐药的NSCLC患者的潜在诊断和治疗靶标。Linc00221促进了NSCLC的顺铂耐药性，而miR-519a是Linc00221的直接靶标。另外，miR-519a可以通过靶向ZBTB5来促进NSCLC细胞中的顺铂敏感性。Linc00221可以通过吸附miR-519a来阻止其对ZBTB5的下调，从而介导NSCLC的顺铂敏感性。总之，Linc00221通过下游miR-519a / ZBTB5信号传导轴促进NSCLC的顺铂耐药性，可用作临床对顺铂耐药的NSCLC患者的潜在诊断和治疗靶标。