Medical College of Guangxi University, Nanning, Guangxi, PR China.
School of Basic Medical Sciences, Youjiang Medical University for Nationalities, Baise, Guangxi, PR China.
Cell Cycle. 2022 May;21(9):948-960. doi: 10.1080/15384101.2022.2035617. Epub 2022 Feb 1.
Proteins of the RNF183 (RING finger 183) family proteins have been reported to be of great importance in tumor the initiation and progression. However, the biological role and regulatory mechanism of RNF183 in non small cell lung cancer (NSCLC) development and progression are poorly defined. Hence, lung adenocarcinoma (LUAD) cell proliferation, cell apoptosis and cell cycle were measured using Cell Counting Kit-8 and flow cytometry analysis, respectively. The correlation between RNF183 and SHP2 (Src homology-2 domain-containing protein tyrosine phosphatase) was measured using coimmunoprecipitation and ubiquitination analysis . Tumor growth of NSCLC cells was measured using the nude mouse xenograft model. In this study, we verify that elevated RNF183 expression in tumor tissues of LUAD, origin from the TCGA, GEPIA, TIMER, and UALCAN database. RNF183 regulates apoptosis and cell cycle and tumor growth by activating the STAT3 pathway through ubiquitination of SHP2, a negative feedback regulator of the STAT3 pathway. Taken together, our results demonstrate that RNF183 regulates proliferation, apoptosis, and cell cycle in LUAD cells modulation of SHP2/STAT3 signaling, suggesting the potential for targeting the RNF183-SHP2/STAT3 pathway for use in LUAD treatment.
RNF183（环指蛋白 183）家族蛋白在肿瘤的发生和发展中具有重要意义。然而，RNF183 在非小细胞肺癌（NSCLC）发展和进展中的生物学作用和调节机制仍不清楚。因此，分别使用细胞计数试剂盒-8 和流式细胞术分析来测量 RNF183 对肺腺癌细胞增殖、细胞凋亡和细胞周期的影响。使用免疫共沉淀和泛素化分析来测量 RNF183 与 SHP2（Src 同源性-2 结构域含有蛋白酪氨酸磷酸酶）之间的相关性。使用裸鼠异种移植模型来测量 NSCLC 细胞的肿瘤生长。在这项研究中，我们验证了来自 TCGA、GEPIA、TIMER 和 UALCAN 数据库的 LUAD 肿瘤组织中 RNF183 表达升高。RNF183 通过泛素化 STAT3 通路的负反馈调节剂 SHP2，调节细胞凋亡和细胞周期，并通过激活 STAT3 通路来调节肿瘤生长。总之，我们的研究结果表明，RNF183 通过调节 SHP2/STAT3 信号通路来调节 LUAD 细胞的增殖、凋亡和细胞周期，提示靶向 RNF183-SHP2/STAT3 通路用于 LUAD 治疗的潜力。
