Knockdown of lncRNA LEF1-AS1 inhibited the progression of oral squamous cell carcinoma (OSCC) via Hippo signaling pathway
Knockdown of lncRNA LEF1-AS1 inhibited the progression of oral squamous cell carcinoma (OSCC) via Hippo signaling pathway
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DOI：
10.1080/15384047.2019.1599671
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发表时间：
2019-04-14
影响因子：
3.6
通讯作者：
Chen, Yangzong
中科院分区：
文献类型：
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作者：
Zhang, Chanqiong;Bao, Chunchun;Chen, Yangzong
已证实长链非编码RNA（lncRNA）在多种癌症中发挥着至关重要的作用。 LncRNA LEF1-AS1 是结直肠癌和胶质母细胞瘤中报道的癌基因。在这项研究中，我们发现 LEF1-AS1 在口腔鳞状细胞癌 (OSCC) 组织和细胞系中显着增加。此外，LEF1-AS1水平高的OSCC患者预后较差。从功能上讲，LEF1-AS1敲低可抑制细胞存活、增殖和迁移，而增强细胞凋亡并诱导体外G0/G1细胞周期停滞。一致地，LEF1-AS1沉默阻碍了体内肿瘤的生长。此外，LEF1-AS1抑制通过直接与LATS1相互作用刺激Hippo信号通路的激活。此外，我们发现LEF1-AS1沉默消除了LEF1-AS1与LATS1的相互作用，同时增强了LATS1与MOB的结合，因此促进YAP磷酸化但损害YAP1核转位。此外，我们证明 LEF1-AS1 通过 LATS1 依赖性方式调节 YAP1 易位。此外，我们还发现 YAP1 过表达消除了 LEF1-AS1 抑制对 OSCC 细胞生物学过程的抑制作用。总之，我们得出结论，LEF1-AS1 通过与 LATS1 相互作用抑制 Hippo 信号通路，在 OSCC 中发挥致癌作用，这表明 LEF1-AS1 在 OSCC 中具有治疗和预后潜力。
It is verified that long non-coding RNAs (lncRNAs) play crucial roles in various cancers. LncRNA LEF1-AS1 is a reported oncogene in colorectal cancer and glioblastoma. In this study, we unveiled that LEF1-AS1 markedly increased in oral squamous cell carcinoma (OSCC) tissues and cell lines. Besides, OSCC patients with high levels of LEF1-AS1 were apt to poor prognosis. Functionally, LEF1-AS1 knockdown inhibited cell survival, proliferation and migration, whereas enhanced cell apoptosis and induced G0/G1 cell cycle arrest in vitro. Consistently, LEF1-AS1 silence hindered tumor growth in vivo. Moreover, LEF1-AS1 inhibition stimulated the activation of Hippo signaling pathway through directly interacting with LATS1. Furtherly, we disclosed that LEF1-AS1 silence abolished the interaction of LEF1-AS1 with LATS1 while enhanced the binding of LATS1 to MOB, therefore promoting YAP phosphorylation but impairing YAP1 nuclear translocation. Additionally, we demonstrated that LEF1-AS1 regulated YAP1 translocation via a LATS1-dependent manner. Furthermore, we also uncovered that YAP1 overexpression abolished the suppressive impact of LEF1-AS1 repression on the biological processes of OSCC cells. In a word, we concluded that LEF1-AS1 served an oncogenic part in OSCC through suppressing Hippo signaling pathway by interacting with LATS1, suggesting the therapeutic and prognostic potential of LEF1-AS1 in OSCC.