三阴性乳腺癌
癌症研究
Wnt信号通路
泛素连接酶
泛素
生物
癌基因
乳腺癌
非翻译区
癌症
信使核糖核酸
信号转导
细胞生物学
遗传学
细胞周期
基因
作者
Duanyang Zhai,Mengmeng Zhang,Yuying Li,Jiong Bi,Xiaying Kuang,Shan Zhang,Nan Shao,Ying Lin
出处
期刊:Cancer Letters
[Elsevier]
日期:2022-09-01
卷期号:544: 215797-215797
被引量:5
标识
DOI:10.1016/j.canlet.2022.215797
摘要
Long intergenic nonprotein coding RNA 1194 (LINC01194) has been reported as an oncogene in several cancer types, but its expression and potential role in triple-negative breast cancer (TNBC) are still unclear. We found that LINC01194 was significantly highly expressed in TNBC based on The Cancer Genome Atlas (TCGA) database. Data from in vitro experiments and in vivo assays demonstrated that LINC01194 promoted TNBC progression. Through bioinformatics prediction, mass spectrometry, and mechanical experiments, we found that LINC01194 could recruit nuclear mitotic apparatus protein 1 (NUMA1) to bind to the untranslated region (3′UTR) of ubiquitin-conjugating enzyme E2 C (UBE2C) 3′ and stabilize UBE2C mRNA. Moreover, we found that UBE2C acted as an ubiquitin ligase to promote the ubiquitination and degradation of ryanodine receptor type 2 (RYR2) that inhibited the progression of TNBC by inhibiting the Wnt/β-catenin signaling pathway. In summary, LINC01194 activate the Wnt/β-catenin signaling pathway and accelerates the malignant progression of TNBC by recruiting NUMA1 to stabilize UBE2C mRNA and thus promotes RYR2 ubiquitination and degradation. These findings might provide a more effective therapeutic strategy for TNBC patients.
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