Department of Chest Surgery, Nanyang City Center Hospital, Nanyang, China.
Department of Respiration, Jinshan Hospital Affiliated to Fudan University, Shanghai, China.
J Cell Physiol. 2018 Sep;233(9):7164-7172. doi: 10.1002/jcp.26543. Epub 2018 Apr 6.
Long non-coding RNAs (lncRNAs) have been validated to play important role in multiple cancers, including non-small cell lung cancer (NSCLC). In present study, our team investigate the biologic role of SNHG15 in the NSCLC tumorigenesis. LncRNA SNHG15 was significantly upregulated in NSCLC tissue samples and cells, and its overexpression was associated with poor prognosis of NSCLC patients. In vitro, loss-of-functional cellular experiments showed that SNHG15 silencing significantly inhibited the proliferation, promoted the apoptosis, and induced the cycle arrest at G0//G1 phase. In vivo, xenograft assay showed that SNHG15 silencing suppressed tumor growth of NSCLC cells. Besides, SNHG15 silencing decreased CDK14 protein expression both in vivo and vitro. Bioinformatics tools and luciferase reporter assay confirmed that miR-486 both targeted the 3'-UTR of SNHG15 and CDK14 and was negatively correlated with their expression levels. In summary, our study conclude that the ectopic overexpression of SNHG15 contribute to the NSCLC tumorigenesis by regulating CDK14 protein via sponging miR-486, providing a novel insight for NSCLC pathogenesis and potential therapeutic strategy for NSCLC patients.
长链非编码 RNA（lncRNAs）已被证实在多种癌症中发挥重要作用，包括非小细胞肺癌（NSCLC）。在本研究中，我们团队研究了 SNHG15 在 NSCLC 肿瘤发生中的生物学作用。lncRNA SNHG15 在 NSCLC 组织样本和细胞中显著上调，其过表达与 NSCLC 患者的不良预后相关。在体外，功能丧失性细胞实验表明，SNHG15 沉默显著抑制增殖，促进凋亡，并诱导细胞周期停滞在 G0//G1 期。在体内，异种移植实验表明，SNHG15 沉默抑制 NSCLC 细胞的肿瘤生长。此外，SNHG15 沉默在体内和体外均降低了 CDK14 蛋白的表达。生物信息学工具和荧光素酶报告基因实验证实 miR-486 既靶向 SNHG15 的 3'-UTR，也靶向 CDK14，且与它们的表达水平呈负相关。综上所述，我们的研究表明，SNHG15 的异位过表达通过海绵吸附 miR-486 来调节 CDK14 蛋白，从而促进 NSCLC 的发生，为 NSCLC 的发病机制提供了新的见解，并为 NSCLC 患者提供了潜在的治疗策略。
