研究动态
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人类抗原 R 敲除可通过基质金属蛋白酶-1 基因表达失活来减弱口腔癌细胞的侵袭活性。

Human antigen R knockdown attenuates the invasive activity of oral cancer cells through inactivation of matrix metalloproteinase-1 gene expression.

发表日期:2024 Jan
作者: Wataru Kakuguchi, Tetsuya Kitamura, Tomomi Takahashi, Aya Yanagawa-Matsuda, Chih-Yuan Fang, Yoichi Ohiro, Fumihiro Higashino
来源: Journal of Dental Sciences

摘要:

RNA 结合蛋白人类抗原 R (HuR) 识别 mRNA 3'-非翻译区中富含 AU 的元件。细胞质HuR的表达与多种肿瘤的恶性程度相关。本研究的目的是调查HuR敲低对口腔癌侵袭活性的影响。进行增殖、侵袭、实时PCR和报告基因检测以证实HuR敲低可下调癌细胞的侵袭活性。对高侵袭性癌、鳞状细胞癌(SCC)和低侵袭性癌、疣状癌(VC)进行免疫组织化学染色,以确定细胞质HuR的定位是否与基质金属蛋白酶-1(MMP-1)表达相关。侵袭活性HuR 敲低癌细胞中的表达显着低于对照细胞。荧光素酶检测显示 HuR 敲低使 MMP-1 基因的启动子活性失活。在 HuR 敲低的癌细胞中,MMP-1 表达所需的转录因子(包括 c-fos 和 c-jun)的 mRNA 水平降低。免疫组织化学分析显示,浸润性癌中细胞质HuR和MMP-1的水平高于低浸润性癌。 HuR 在大多数 SCC 病例的侵袭前沿诱导 MMP-1 表达。HuR 敲低通过降低 MMP-1 的表达(至少部分降低)来减弱癌细胞的侵袭活性。 HuR定位可能有助于确定癌细胞的侵袭表型并抑制癌细胞侵袭。此外,在口腔鳞状细胞癌中,HuR 可能通过 MMP-1 的表达与侵袭活动相关。© 2023 Association for Dental Sciences of the Republic of China。 Elsevier B.V. 的出版服务
The RNA-binding protein human antigen R (HuR) recognizes AU-rich elements in the 3'-untranslated regions of mRNA. The expression of cytoplasmic HuR is related to the malignancy of many carcinomas. The aim of this study is investigation of effect of HuR knockdown for invasive activity of oral carcinoma.Proliferation, invasion, real-time PCR, and reporter gene assays were performed to confirm that the knockdown of HuR downregulates the invasive activity of cancer cells. Immunohistochemical staining was performed for high invasive carcinoma, squamous cell carcinoma (SCC) and low invasive carcinoma, verrucous carcinoma (VC), to determine if the localization of cytoplasmic HuR is related to matrix metalloproteinase-1 (MMP-1) expression.Invasive activity was significantly lower in HuR knockdown cancer cells than in control cells. A luciferase assay revealed that HuR knockdown inactivated the promoter activity of the MMP-1 gene. The mRNA levels of the transcription factors required for MMP-1 expression, including c-fos and c-jun, were decreased in HuR knockdown cancer cells. Immunohistochemical analysis revealed the level of cytoplasmic HuR and MMP-1 in invasive carcinoma to be higher than in low invasive cancer. HuR induced MMP-1 expression in the invasive front of most SCC cases.HuR knockdown attenuated the invasive activity of cancer cells by decreasing the expression of the MMP-1, at least partially. HuR localization may help determine the invasive phenotype of cancer cells and inhibit cancer cell invasion. Furthermore, in oral SCC, HuR may be related to invasive activity through the expression of MMP-1.© 2023 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V.