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RIG-I 通过促进 p21 降解促进食管鳞状细胞癌的细胞增殖。

RIG-I promotes cell proliferation in esophageal squamous cell carcinoma by facilitating p21 degradation.

机构信息

Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, China.

Department of Oncology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, No.136 Jingzhou Street, Xiangyang, Hubei, 441021, China.

出版信息

Med Oncol. 2023 Sep 1;40(10):288. doi: 10.1007/s12032-023-02157-9.

DOI:10.1007/s12032-023-02157-9
PMID:37656315
Abstract

Retinoic acid-inducible gene-I (RIG-I) is considered a key sensor for host recognition of RNA virus infections. Recent studies have shown that RIG-I also regulates carcinogenesis. However, the role of RIG-I in esophageal squamous cell carcinoma (ESCC) remains unclear. We investigated the RIG-I expression in ESCC cells using a public database, immunohistochemistry, and Western blotting. We evaluated the proliferative activity of ESCC cells using CCK-8, colony formation, and EdU staining assays. Further, we determined the ESCC cell-cycle changes using flow cytometry and the ubiquitination of p21 in the cells using cycloheximide chase and ubiquitination assays. Finally, we verified the in vivo effects of RIG-I on ESCC cells by constructing xenograft models. RIG-I was highly expressed in ESCC cells and significantly promoted their proliferation and cell-cycle. Moreover, RIG-I knockdown inhibited xenograft growth in nude mice. Furthermore, RIG-I accelerated the cell-cycle by promoting the ubiquitination and degradation of p21. Overall, this study revealed that the increased expression of RIG-I due to ESCC accelerated the progression of esophageal cancer by promoting the ubiquitination and degradation of p21, which is related to the prognosis of ESCC. Thus, RIG-I may be a novel therapeutic target for ESCC treatment.

摘要

维甲酸诱导基因-I(RIG-I)被认为是宿主识别 RNA 病毒感染的关键传感器。最近的研究表明,RIG-I 还调节致癌作用。然而,RIG-I 在食管鳞状细胞癌(ESCC)中的作用尚不清楚。我们使用公共数据库、免疫组织化学和 Western blot 研究了 RIG-I 在 ESCC 细胞中的表达。我们使用 CCK-8、集落形成和 EdU 染色测定评估 ESCC 细胞的增殖活性。进一步,我们使用流式细胞术确定细胞周期变化,并使用环己酰亚胺追踪和泛素化测定确定细胞中 p21 的泛素化。最后,我们通过构建异种移植模型验证了 RIG-I 对 ESCC 细胞的体内作用。RIG-I 在 ESCC 细胞中高表达,显著促进其增殖和细胞周期。此外,RIG-I 敲低抑制了裸鼠异种移植瘤的生长。此外,RIG-I 通过促进 p21 的泛素化和降解加速细胞周期。总之,这项研究表明,由于 ESCC 导致的 RIG-I 表达增加通过促进 p21 的泛素化和降解加速食管癌的进展,与 ESCC 的预后相关。因此,RIG-I 可能是 ESCC 治疗的一个新的治疗靶点。

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