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WDR5 通过 CARM1/β-catenin 轴促进口腔鳞状细胞癌的肿瘤发生。

WDR5 promotes the tumorigenesis of oral squamous cell carcinoma via CARM1/β-catenin axis.

机构信息

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, No. 14 Renmin South Road, Chengdu, 610065, People's Republic of China.

Sichuan University, Chengdu, 610065, People's Republic of China.

出版信息

Odontology. 2022 Jan;110(1):138-147. doi: 10.1007/s10266-021-00649-6. Epub 2021 Aug 16.

Abstract

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 β-catenin signaling pathway, while this phenomenon was restored by CARM1 overexpression. Silencing of WDR5 attenuated the tumorigenesis of OSCC via CARM1/β-catenin axis. Thus, WDR5 might be a target for OSCC treatment.

摘要

口腔鳞状细胞癌(OSCC)是一种全球性的恶性肿瘤。WD 重复结构域 5(WDR5)参与癌症的进展。此外,有报道称 WDR5 在头颈部癌症中上调,但其在 OSCC 中的作用尚不清楚。首先,通过 qRT-PCR、IHF 和 western blot 检测口腔癌组织和细胞中 WDR5 的表达。通过 CCK-8 检测细胞活力。通过 Transwell 检测细胞迁移。在口腔癌细胞中敲低 WDR5 或 CARM1,以检测其对癌症生长的功能。在 OSCC 中,WDR5 和 CARM1 显著上调。沉默 WDR5 抑制 OSCC 细胞活力和迁移。下调 WDR5 显著抑制 OSCC 细胞中 CARM1 的水平,而 CARM1 的升高可以挽救 WDR5 敲低对 OSCC 肿瘤发生的影响。此外,沉默 WDR5 显著抑制β-连环蛋白信号通路,而 CARM1 的过表达则恢复了这种现象。沉默 WDR5 通过 CARM1/β-连环蛋白轴减弱了 OSCC 的肿瘤发生。因此,WDR5 可能是 OSCC 治疗的靶点。

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