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EIF4A3介导的circPRKCI表达通过调节WBP2和PI3K/AKT信号通路促进三阴性乳腺癌进展。

EIF4A3-mediated circPRKCI expression promotes triple-negative breast cancer progression by regulating WBP2 and PI3K/AKT signaling pathway.

作者信息

Wang Xuehui, Song Hongming, Fang Lin, Wu Tianqi

机构信息

Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China.

Department of Breast and Thyroid Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.

出版信息

Cell Death Discov. 2022 Mar 2;8(1):92. doi: 10.1038/s41420-022-00892-y.

Abstract

Triple-negative breast cancer (TNBC) is known as a highly aggressive subtype of BC due to high rate of recurrence and metastasis, poor prognosis and lacking of effective targeted therapies. Circular RNAs (circRNAs) have been reported to participate in the progression of TNBC. In this study, we demonstrated that circPRKCI, derived from the PRKCI gene, was elevated in BC tissues and cell lines, especially in TNBC. The functional investigation showed that circPRKCI could significantly promote the proliferation and migration of TNBC in vivo and in vitro. In addition, circPRKCI regulated WBP2 and the phosphorylation of AKT via serving as miR-545-3p sponge. Of note, EIF4A3 could induce circPRKCI expression and nuclear export in TNBC cells. Taken together, EIF4A3-mediated circPRKCI could promote TNBC progression by regulating WBP2 and PI3K/AKT signaling pathway, providing a new avenue of therapy for TNBC.

摘要

三阴性乳腺癌(TNBC)因其高复发率和转移率、预后差以及缺乏有效的靶向治疗方法,而被认为是一种侵袭性很强的乳腺癌亚型。据报道,环状RNA(circRNAs)参与了TNBC的进展。在本研究中,我们证明了源自PRKCI基因的circPRKCI在乳腺癌组织和细胞系中升高,尤其是在TNBC中。功能研究表明,circPRKCI在体内和体外均可显著促进TNBC的增殖和迁移。此外,circPRKCI通过充当miR-545-3p海绵来调节WBP2和AKT的磷酸化。值得注意的是,EIF4A3可诱导TNBC细胞中circPRKCI的表达和核输出。综上所述,EIF4A3介导的circPRKCI可通过调节WBP2和PI3K/AKT信号通路促进TNBC进展,为TNBC提供了一条新的治疗途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2570/8891274/96981d1ace4f/41420_2022_892_Fig1_HTML.jpg

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