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The circRNA circIFI30 promotes progression of triple-negative breast cancer and correlates with prognosis

机译:circRNA circIFI30促进三阴性乳腺癌的进展并与预后相关

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摘要

Growing evidence suggests that circRNAs exert a critical role in tumorigenesis and cancer progression. To date, the molecular mechanisms underlying circRNAs in triple-negative breast cancer (TNBC) are still poorly known. Here, circRNA expression profile was investigated by RNA sequencing in TNBC tissues and matched para-carcinoma tissues. We found that circIFI30 was significantly up-regulated in TNBC tissues and cells using quantitative real-time PCR and in situ hybridization. High circIFI30 expression was positively correlated with clinical TNM stage, pathological grade and poor prognosis of TNBC patients. Functionally, a series of and experiments showed that knockdown of circIFI30 could markedly inhibit TNBC cell proliferation, migration, invasion and cell cycle progression, induce apoptosis as well as suppress tumorigenesis and metastasis. Up-regulation of circIFI30 exerted an opposite effect. Mechanistically, we demonstrated that circIFI30 might act as a competing endogenous RNA (ceRNA) of miR-520b-3p to abolish the suppressive effect on target gene CD44 by fluorescent in situ hybridization (FISH), dual luciferase reporter assay, RNA immunoprecipitation and RNA pull-down assays. Therefore, our work uncovers the mechanism by which circIFI30 could promote TNBC progression through circIFI30/miR-520b-3p/CD44 axis and circIFI30 could be a novel diagnostic/prognostic marker and therapeutic target for TNBC patients.
机译:越来越多的证据表明,circRNA在肿瘤发生和癌症进展中起关键作用。迄今为止,三阴性乳腺癌(TNBC)中circRNA的分子机制仍知之甚少。在这里,通过RNA测序在TNBC组织和匹配的癌旁组织中研究了circRNA表达谱。我们发现,使用定量实时PCR和原位杂交技术,在TNBC组织和细胞中circIFI30明显上调。 circIFI30的高表达与TNBC患者的临床TNM分期,病理分级和预后不良呈正相关。在功能上,一系列的实验表明,敲除circIFI30可以显着抑制TNBC细胞的增殖,迁移,侵袭和细胞周期进程,诱导凋亡,并抑制肿瘤发生和转移。 circIFI30的上调发挥相反的作用。从机制上讲,我们证明了circIFI30可能充当miR-520b-3p的竞争内源性RNA(ceRNA),以通过荧光原位杂交(FISH),双重荧光素酶报道基因分析,RNA免疫沉淀和RNA拉动消除对靶基因CD44的抑制作用。向下测定。因此,我们的工作揭示了circIFI30可以通过circIFI30 / miR-520b-3p / CD44轴促进TNBC进展的机制,而circIFI30可以作为TNBC患者的新型诊断/预后标志物和治疗靶标。

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