circ-EIF6 encodes EIF6-224aa to promote TNBC progression via stabilizing MYH9 and activating the Wnt/beta-catenin pathway
circ-EIF6 encodes EIF6-224aa to promote TNBC progression via stabilizing MYH9 and activating the Wnt/beta-catenin pathway
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circ-EIF6 编码 EIF6-224aa，通过稳定 MYH9 和激活 Wnt/β-catenin 通路促进 TNBC 进展
DOI：
10.1016/j.ymthe.2021.08.026
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发表时间：
2022-01-05
影响因子：
12.4
通讯作者：
Yang, Qifeng
中科院分区：
文献类型：
--
作者：
Li, Yaming;Wang, Zekun;Yang, Qifeng
环状RNA（circular RNA，circRNA）的蛋白质编码能力是近年来研究的热点，但其在三阴性乳腺癌（triple-negative breast cancer，TNBC）中的表达及其作用尚不清楚。通过交叉来自临床样品和细胞系的circRNA测序数据，我们鉴定了一种称为circ-EIF 6的circRNA，其预测了TNBC患者队列中较差的预后并与临床病理特征相关。在功能上，我们表明circ-EIF 6在体外和体内促进TNBC细胞的增殖和转移。从机制上讲，我们发现circ-EIF 6包含一个675个核苷酸（nt）的开放阅读框（ORF），并且来自ATG的约150-bp序列作为内部核糖体进入位点（IRES）发挥作用，这是50个帽非依赖性编码RNA翻译起始所必需的。circ-EIF 6编码一种新的肽，称为EIF 6 -224氨基酸（aa），其负责circ-EIF 6的致癌作用。内源性和组织特异性抗体。此外，EIF 6 - 224 aa直接与乳腺癌中的癌基因MYH 9相互作用，并通过抑制泛素-蛋白酶体途径并随后激活Wnt/β-连环蛋白途径来减少MYH 9降解。我们的研究为TNBC患者的定制治疗提供了新的见解，作为一种新的有前途的预后和治疗靶点。
The protein-coding ability of circular RNAs (circRNAs) has recently been a hot topic, but the expression and roles of protein-coding circRNAs in triple-negative breast cancer (TNBC) remain uncertain. By intersecting circRNA sequencing data from clinical samples and cell lines, we identified a circRNA, termed circ-EIF6, which predicted a poorer prognosis and correlated with clinicopathological characteristics in a cohort of TNBC patients. Functionally, we showed that circ-EIF6 promoted the proliferation and metastasis of TNBC cells in vitro and in vivo. Mechanistically, we found that circ-EIF6 contains a 675-nucleotide (nt) open reading frame (ORF) and that the -150-bp sequence from ATG functioned as an internal ribosome entry site (IRES), which is required for translation initiation in 50 cap-independent coding RNAs. circ-EIF6 encodes a novel peptide, termed EIF6-224 amino acid (aa), which is responsible for the oncogenic effects of circ-EIF6. The endogenous and tissues by specific antibody. Moreover, EIF6-224aa directly interacted with MYH9, an oncogene in breast cancer, and decreased MYH9 degradation by inhibiting the ubiquitin-proteasome pathway and subsequently activating the Wnt/beta-catenin pathway. Our study provided novel insights into the roles of as a novel promising prognostic and therapeutic target for tailored therapy in TNBC patients.