Gao Ling, Cao Hua, Cheng Xiulian
Department of Otorhinolaryngology, The First Affiliated Hospital of Zhengzhou University Zhengzhou 450052, Henan Province, PR China.
Am J Cancer Res. 2018 Sep 1;8(9):1712-1724. eCollection 2018.
Laryngeal squamous cell carcinoma (LSCC) is the second highest incidence among the head and neck malignancies. Long noncoding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1) functions as an oncogene in various human cancers. However, the biological functions and molecular mechanisms of SNHG1 in LSCC have not been reported. In this study, we found that lncRNA SNHG1 is significantly upregulated in LSCC and associated with prognosis of LSCC patients. Knockdown of SNHG1 inhibited cell proliferation, migration and invasion and induced cell apoptosis. In addition, knockdown of SNHG1 inhibits LSCC growth and metastasis . Mechanistically, SNHG1 promotes YAP1 expression and Hippo signaling activity by competitively sponging miR-375. Moreover, YAP1 could occupy the SNHG1 promoter to enhance its transcription, suggesting that there exists a positive feedback regulation between YAP1 and SNHG1. Collectively, our study first elucidates the mechanism of SNHG1-mediated malignant phenotypes through evoking the miR-375/YAP1/Hippo signalling axis, which provides a novel target for LSCC treatment.
喉鳞状细胞癌（LSCC）是头颈部恶性肿瘤中发病率第二高的癌症。长链非编码RNA（lncRNA）小核仁RNA宿主基因1（SNHG1）在多种人类癌症中发挥癌基因的作用。然而，SNHG1在LSCC中的生物学功能和分子机制尚未见报道。在本研究中，我们发现lncRNA SNHG1在LSCC中显著上调，且与LSCC患者的预后相关。敲低SNHG1可抑制细胞增殖、迁移和侵袭，并诱导细胞凋亡。此外，敲低SNHG1可抑制LSCC的生长和转移。机制上，SNHG1通过竞争性结合miR-375促进YAP1表达和Hippo信号活性。此外，YAP1可占据SNHG1启动子以增强其转录，提示YAP1与SNHG1之间存在正反馈调节。总体而言，我们的研究首次阐明了SNHG1通过激活miR-375/YAP1/Hippo信号轴介导恶性表型的机制，为LSCC治疗提供了新的靶点。
