Department of Thoracic Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province 130033, P.R. China.
Department of Oncology, The First Hospital of Jilin University, Changchun, Jilin Province 130021, P.R. China.
Biosci Rep. 2018 Aug 29;38(4). doi: 10.1042/BSR20180400. Print 2018 Aug 31.
Gefitinib resistance is one of the major obstacles for the treatment of lung adenocarcinoma (LAD). The present study aimed to investigate the effects of the long non-coding RNA (lncRNA), small nucleolar RNA host gene 5SNHG5 on gefitinib resistance in LAD and explore the underlying mechanisms. The quantitative real-time PCR (qRT-PCR) results showed that SNHG5 expression was significantly down-regulated in LAD patients with acquired gefitinib resistance and gefitinib resistant LAD cell lines. SNHG5 overexpression sensitized gefitinib resistant LAD cells to gefitinib treatment, while knockdown of SNHG5 rendered gefitinib sensitive LAD cells to gefitinib treatment. Bioinformatics analysis showed that SNHG5 exerted its function through interaction with , which was further confirmed by luciferase reporter assay in 293T cells. Overexpression of SNHG5 suppressed the expression of , while the knockdown of SNHG5 increased the expression. expression was significantly up-regulated in LAD specimens with acquired gefitinib resistance and was negatively correlated with SNHG5 expression. In addition, CASP1 was predicted as a downstream target of Overexpression of suppressed the expression of CASP1 in PC9 cells and knockdown of increased the CASP1 expression in PC9GR cells. functional assay showed that knockdown of CASP1 in SNHG5-overexpressed PC9GR cells abolished their gefitinib resistance. Overall, the present study demonstrated, for the first time, that the SNHG5//CASP1 axis functions as an important role in LAD cells gefitinib resistance and potentially contributes to the improvement of LAD diagnosis and therapy.
吉非替尼耐药是肺腺癌（LAD）治疗的主要障碍之一。本研究旨在探讨长链非编码 RNA（lncRNA），小核仁 RNA 宿主基因 5SNHG5 对 LAD 中吉非替尼耐药的影响，并探讨其潜在机制。实时荧光定量 PCR（qRT-PCR）结果显示，获得性吉非替尼耐药的 LAD 患者和吉非替尼耐药 LAD 细胞系中 SNHG5 表达明显下调。SNHG5 过表达使吉非替尼耐药 LAD 细胞对吉非替尼治疗敏感，而 SNHG5 敲低使吉非替尼敏感 LAD 细胞对吉非替尼治疗敏感。生物信息学分析表明，SNHG5 通过与相互作用发挥其功能，这在 293T 细胞中的荧光素酶报告基因实验中得到进一步证实。SNHG5 过表达抑制 表达，而 SNHG5 敲低增加 表达。获得性吉非替尼耐药的 LAD 标本中 表达明显上调，与 SNHG5 表达呈负相关。此外，预测 CASP1 是 的下游靶基因。过表达 抑制 PC9 细胞中 CASP1 的表达，而敲低 增加 PC9GR 细胞中 CASP1 的表达。功能测定表明，在 SNHG5 过表达的 PC9GR 细胞中敲低 CASP1 可消除其吉非替尼耐药性。总之，本研究首次表明，SNHG5//CASP1 轴在 LAD 细胞吉非替尼耐药中起重要作用，并可能有助于改善 LAD 的诊断和治疗。
