Department of Respiratory and Critical Care Medicine, Yinzhou People's Hospital, Yinzhou Hospital Affiliated to Medical School of Ningbo University, Ningbo, P.R. China.
Department of Nephrology, Yinzhou People's Hospital, Yinzhou Hospital Affiliated to Medical School of Ningbo University, Ningbo, P.R. China.
Oncol Res. 2019 May 7;27(5):623-628. doi: 10.3727/096504018X15420734828058. Epub 2019 Feb 14.
Circular RNAs (circRNAs) represent a new class of noncoding RNAs that is involved in the development of cancer. However, little is known about their role in chemoresistance. In the present study, we found that hsa_circ_0003998 expression levels in lung adenocarcinoma (LAD) tissues and docetaxel-resistant cell lines (A549/DTX and H1299/DTX) were upregulated. Knockdown of hsa_circ_0003998 decreased chemoresistance, inhibited proliferation, and enhanced apoptosis in docetaxel-resistant LAD cells. Moreover, by using bioinformatics and luciferase reporter assays, we found that miR-326 was a direct target of hsa_circ_0003998. Functional analysis revealed that miR-326 mediated the effect of hsa_circ_0003998 on chemosensitivity. Our findings provide a molecular insight on understanding drug resistance in LAD cells. Therefore, inactivation of hsa_circ_0003998 or activation of miR-326 could be a novel approach for the treatment of LAD.
环状 RNA（circRNAs）是一类新的非编码 RNA，参与癌症的发生发展。然而，其在化疗耐药中的作用知之甚少。本研究发现，肺腺癌（LAD）组织和多西紫杉醇耐药细胞系（A549/DTX 和 H1299/DTX）中 hsa_circ_0003998 的表达水平上调。hsa_circ_0003998 的敲低降低了多西紫杉醇耐药 LAD 细胞的化疗耐药性，抑制了增殖，并增强了细胞凋亡。此外，通过生物信息学和荧光素酶报告基因检测，我们发现 miR-326 是 hsa_circ_0003998 的直接靶标。功能分析表明，miR-326 介导了 hsa_circ_0003998 对化疗敏感性的影响。我们的研究结果为理解 LAD 细胞耐药性提供了分子见解。因此，hsa_circ_0003998 的失活或 miR-326 的激活可能成为治疗 LAD 的新方法。
