WDR5 promotes the tumorigenesis of oral squamous cell carcinoma via CARM1/β-catenin axis
WDR5 promotes the tumorigenesis of oral squamous cell carcinoma via CARM1/β-catenin axis
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WDR5 通过 CARM1/β-连环蛋白轴促进口腔鳞状细胞癌的肿瘤发生。
DOI：
10.1007/s10266-021-00649-6
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发表时间：
2021-08-16
期刊：
影响因子：
2.5
通讯作者：
Yang, Ran
中科院分区：
文献类型：
--
作者：
Lyu, Xiao-Ying;Shui, Yu-Sen;Yang, Ran
口腔鳞状细胞癌(OSCC)是一种世界性的恶性肿瘤。WD重复结构域5(WDR5)与肿瘤的进展有关。此外，有报道称WDR5在头颈癌中表达上调，而其在口腔鳞癌中的作用尚不清楚。首先，采用定量逆转录聚合酶链式反应、免疫印迹和免疫印迹等方法检测WDR5在口腔癌组织和细胞中的表达。CCK-8比色法检测细胞活力。Transwell法检测细胞迁移情况。通过下调口腔癌细胞中的WDR5或CARM1来检测其对肿瘤生长的作用，WDR5和CARM1在口腔鳞癌中显著上调。沉默WDR5可抑制口腔鳞癌细胞的存活和迁移。WDR5下调可显著抑制口腔鳞癌细胞中CARM1的表达，上调CARM1可挽救WDR5基因下调在口腔鳞癌发生发展中的作用。此外，WDR5的沉默显著失活了β-连环蛋白信号通路，而CARM1的过表达则恢复了这一现象。沉默WDR5可通过CARM1/β-catenin轴抑制口腔鳞癌的发生。因此，WDR5可能是口腔鳞癌治疗的靶点。
Oral squamous cell carcinoma (OSCC) is a malignancy all over the world. WD repeat domain 5 (WDR5) is involved in cancer progression. In addition, it was reported that WDR5 is upregulated in head and neck cancer, while its role in OSCC is unknown. First, the expression of WDR5 in oral cancer tissues and cells was examined by qRT-PCR, IHF and western blot. CCK-8 assay was performed to test the cell viability. Cell migration was assessed by transwell assay. Knocking down WDR5 or CARM1 in oral cancer cells to detect its function on cancer growth, WDR5 and CARM1 were significantly upregulated in OSCC. Silencing WDR5 suppressed OSCC cell viability and migration. CARM1 level in OSCC cells was significantly inhibited by WDR5 downregulation, and CARM1 elevation could rescue the effect of WDR5 knockdown on tumorigenesis of OSCC. Moreover, silencing of WDR5 notably inactivated beta-catenin signaling pathway, while this phenomenon was restored by CARM1 overexpression. Silencing of WDR5 attenuated the tumorigenesis of OSCC via CARM1/beta-catenin axis. Thus, WDR5 might be a target for OSCC treatment.