BACKGROUND Due to the acquired drug resistance, the potency of cisplatin-based chemotherapy is limited in lung cancer, which is a big obstacle in clinical treatment of lung cancer. Abundant evidence has revealed that circular RNAs (circRNAs) exerted facilitating or suppressive function on the tumorigenesis of multiple cancers. The oncogenic role of circ-ABCB10 in breast cancer and clear cell renal cell carcinoma has been validated in recent researches. However, the regulatory mechanism of circ-ABCB10 and its relation to cellular sensitivity to cisplatin in lung cancer is poorly understood. METHODS The expression and characteristic of circ-ABCB10 were analyzed by RT-qPCR and nucleic acid electrophoresis. CCK-8, colony formation, TUNEL and transwell assays were applied to probe the role of FOXD3-AS1 in lung cancer. The interactions of miR-556-3p with circ-ABCB10 and AK4 were testified by luciferase reporter and RIP assays. RESULTS Circ-ABCB10 was markedly upregulated and featured with loop structure in lung cancer. Circ-ABCB10 depletion suppresses lung cancer progression and sensitizes lung cancer cells to cisplatin. Molecular mechanism assays manifested that circ-ABCB10 bound with miR-556-3p and negatively modulated miR-556-3p expression. Additionally, AK4 was testified to be the downstream target of miR-556-3p. More importantly, rescue assays clarified that upregulation of AK4 could reverse the cisplatin-sensitizing and tumor-suppressing effect of circ-ABCB10 knockdown on lung cancer cells. CONCLUSIONS Circ-ABCB10 knockdown enhances sensitivity of lung cancer cells to cisplatin by targeting miR-556-3p/AK4 axis.

中文翻译：

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敲除circ-ABCB10可通过miR-556-3p / AK4轴促进肺癌细胞对顺铂的敏感性。

背景技术由于获得性耐药性，基于顺铂的化学疗法在肺癌中的作用受到限制，这是肺癌临床治疗中的一大障碍。大量证据表明，环状RNA（circRNA）对多种癌症的发生具有促进或抑制作用。circ-ABCB10在乳腺癌和透明细胞肾细胞癌中的致癌作用已在最近的研究中得到证实。但是，人们对circ-ABCB10的调控机制及其与肺癌细胞对顺铂敏感性的关系了解甚少。方法通过RT-qPCR和核酸电泳分析circ-ABCB10的表达和特征。使用CCK-8，集落形成，TUNEL和transwell分析法检测FOXD3-AS1在肺癌中的作用。miR-556-3p与circ-ABCB10和AK4的相互作用通过荧光素酶报告基因和RIP分析进行了验证。结果Circ-ABCB10在肺癌中明显上调并具有环结构。Circ-ABCB10耗竭抑制肺癌的进展，并使肺癌细胞对顺铂敏感。分子机理分析表明，circ-ABCB10与miR-556-3p结合，并且对miR-556-3p的表达产生负调控。此外，AK4被证明是miR-556-3p的下游靶标。更重要的是，抢救试验明确了AK4的上调可以逆转circ-ABCB10敲除对肺癌细胞的顺铂致敏和肿瘤抑制作用。结论Circ-ABCB10敲低可以通过靶向miR-556-3p / AK4轴来增强肺癌细胞对顺铂的敏感性。