Liu Xinyin, Lu Xiyi, Zhen Fuxi, Jin Shidai, Yu Tongfu, Zhu Quan, Wang Wei, Xu Kun, Yao Jiaqi, Guo Renhua
Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Department of Thoracic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Mol Ther Nucleic Acids. 2019 Jun 7;16:155-161. doi: 10.1016/j.omtn.2019.02.010. Epub 2019 Feb 21.
Gefitinib, a tyrosine kinase inhibitor of epidermal growth factor receptor, has been used as the first choice of treatment for advanced non-small-cell lung cancer. However, during the course of treatment, cancer cells often develop resistance to gefitinib without fully understood mechanisms. In this study, we aimed to elucidate an important role of long intergenic non-coding RNA 00665 in developing resistance to gefitinib in non-small-cell lung cancer. We showed that long intergenic non-coding RNA 00665 expression was significantly upregulated in lung cancer tissues and cells with acquired gefitinib resistance. Long intergenic non-coding RNA 00665 knockdown restored gefitinib sensitivity both in vitro and in vivo by suppressing cell proliferation and inducing apoptosis. Moreover, knockdown of long intergenic non-coding RNA 00665 markedly reduced activation of EGFR and its downstream event protein kinase B (AKT). Moreover, LINC00665 could interact with EZH2 and regulate the phosphatidylinositol 3-kinase (PI3K)/AKT pathway. Thus, our study suggests that long intergenic non-coding RNA 00665 is important for non-small-cell lung cancer to develop drug resistance and might be a potential biomarker for drug resistance and a therapeutic target for non-small-cell lung cancer.
吉非替尼是一种表皮生长因子受体酪氨酸激酶抑制剂，已被用作晚期非小细胞肺癌的首选治疗药物。然而，在治疗过程中，癌细胞常常对吉非替尼产生耐药性，但其机制尚未完全明确。在本研究中，我们旨在阐明长链基因间非编码RNA 00665在非小细胞肺癌对吉非替尼耐药形成中的重要作用。我们发现，在获得性吉非替尼耐药的肺癌组织和细胞中，长链基因间非编码RNA 00665的表达显著上调。敲低长链基因间非编码RNA 00665可通过抑制细胞增殖和诱导凋亡，在体外和体内恢复吉非替尼敏感性。此外，敲低长链基因间非编码RNA 00665可显著降低表皮生长因子受体（EGFR）及其下游事件蛋白激酶B（AKT）的激活。此外，LINC00665可与EZH2相互作用并调节磷脂酰肌醇3激酶（PI3K）/AKT信号通路。因此，我们的研究表明，长链基因间非编码RNA 00665在非小细胞肺癌耐药形成中起重要作用，可能是耐药的潜在生物标志物和非小细胞肺癌的治疗靶点。
