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RNF150 通过抑制 ASK1 泛素化来抑制甲状腺乳头状癌,从而通过失活 p38 信号轴来呈现直接靶标。

RNF150 suppresses papillary thyroid carcinoma with ASK1 ubiquitination presenting a direct target via inactivating p38 signaling axis.

机构信息

Department of Endocrinology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.

Department of Endocrinology, Shanghai Songjiang Jiuting Hospital, Shanghai, China.

出版信息

Cell Biol Int. 2023 Jul;47(7):1198-1208. doi: 10.1002/cbin.12011. Epub 2023 Mar 23.

Abstract

Papillary thyroid carcinoma (PTC) is the most prevalent cancer in endocrine system. However, the pathogenic mechanism underlying tumor recurrence remains unclear. RING finger protein (RNF) family plays a crucial role in cancers whereas the role of RNF150 in PTC requires investigation. Our study aimed to explore the function and molecular mechanism of RNF150 in PTC. Here, we extracted data from The Cancer Genome Atlas-THCA (TCGA-THCA) data set to investigate the expression and prognostic value of RNF150 in THCA. We found that RNF150 was lowly expressed in THCA and its high expression indicated favorable prognosis in THCA patients. RNF150 could inhibit the proliferation of PTC cells and suppress p38 phosphorylation both in vitro and in vivo. Meanwhile, the knockdown of RNF150 significantly promoted the proliferation of PTC cells and the phosphorylation of p38, which could be reversed by p38 inhibitor. Besides, RNF150 could interact with ASK1 and promoted its ubiquitination. The overexpression of ASK1 exerted opposite effects against RNF150 in PTC cells. In PTC specimens, RNF150 and ASK1 shared reversed expression pattern. In conclusion, our study revealed that RNF150 could suppress the proliferation of PTC by inactivating p38 pathway and promoting ASK1 ubiquitination, which provided novel targets for PTC treatment.

摘要

甲状腺乳头状癌(PTC)是内分泌系统最常见的癌症。然而,肿瘤复发的发病机制尚不清楚。RING 指蛋白(RNF)家族在癌症中起着至关重要的作用,而 RNF150 在 PTC 中的作用需要进一步研究。本研究旨在探讨 RNF150 在 PTC 中的功能和分子机制。在这里,我们从癌症基因组图谱-THCA(TCGA-THCA)数据集提取数据,以研究 RNF150 在 THCA 中的表达和预后价值。我们发现 RNF150 在 THCA 中低表达,其高表达提示 THCA 患者预后良好。RNF150 可以在体外和体内抑制 PTC 细胞的增殖并抑制 p38 的磷酸化。同时,RNF150 的敲低显著促进了 PTC 细胞的增殖和 p38 的磷酸化,而 p38 抑制剂可以逆转这种作用。此外,RNF150 可以与 ASK1 相互作用并促进其泛素化。ASK1 的过表达对 PTC 细胞中的 RNF150 产生相反的影响。在 PTC 标本中,RNF150 和 ASK1 的表达模式相反。总之,本研究表明,RNF150 可以通过使 p38 通路失活和促进 ASK1 泛素化来抑制 PTC 细胞的增殖,为 PTC 的治疗提供了新的靶点。

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