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Circ_0008717 Sponges miR-326 to Elevate GATA6 Expression to Promote Breast Cancer Tumorigenicity
Biochemical Genetics ( IF 2.4 ) Pub Date : 2022-08-24 , DOI: 10.1007/s10528-022-10270-z
Ling Yang 1, 2 , Yuxin Chen 1, 2
Affiliation  

Circular RNAs (circRNAs) have been reported to paly roles in the progression and management of breast cancers (BC). This work aimed to detect the role and mechanism of circ_0008717 in BC tumorigenesis. Expression levels of genes and proteins were evaluated by quantitative real-time polymerase chain reaction and western blot. In vitro assays were conducted using cell counting kit-8, colony formation, transwell, tube formation, and flow cytometry assays, respectively. The interaction between miR-326 and circ_0008717 or GATA6 (GATA Binding Protein six) was confirmed by bioinformatics analysis, and dual-luciferase reporter assay and RNA immunoprecipitation assay. The murine xenograft models were established to perform in vivo assay. Circ_0008717 and GATA6 were highly expressed, while miR-326 was lowly expressed in BC tissues and cells. Functionally, knockdown of circ_0008717 not only suppressed breast cancer cell proliferation, angiogenesis, migration, invasion and epithelial–mesenchymal transition (EMT) in vitro, but also hindered tumor growth and EMT process in vivo. Mechanistically, Circ_0008717 directly bound to miR-326, which targeted GATA6. Rescue experiments showed that miR-326 reversed the anticancer action of circ_0008717 knockdown on BC cells. Moreover, miR-326 restoration repressed BC cell growth and metastasis, which were attenuated by GATA6 overexpression. In addition, we also observed that circ_0008717 could regulate GATA6 expression by sponging miR-326. Circ_0008717 promoted breast cancer growth and metastasis through miR-326/GATA6 axis, revealing a potential therapeutic target for breast cancer treatment.



中文翻译:

Circ_0008717 海绵 miR-326 提高 GATA6 表达以促进乳腺癌致瘤性

据报道,环状 RNA (circRNA) 在乳腺癌 (BC) 的进展和管理中发挥作用。本工作旨在检测circ_0008717在BC肿瘤发生中的作用和机制。通过定量实时聚合酶链反应和蛋白质印迹评估基因和蛋白质的表达水平。分别使用细胞计数试剂盒 8、集落形成、transwell、管形成和流式细胞术测定进行体外测定。miR-326 和 circ_0008717 或 GATA6(GATA 结合蛋白六)之间的相互作用通过生物信息学分析、双荧光素酶报告基因分析和 RNA 免疫沉淀分析得到证实。建立小鼠异种移植模型以进行体内测定。Circ_0008717 和 GATA6 在 BC 组织和细胞中高表达,而 miR-326 低表达。在功能上,circ_0008717 的敲低不仅在体外抑制了乳腺癌细胞增殖、血管生成、迁移、侵袭和上皮-间质转化 (EMT),而且在体内也阻碍了肿瘤生长和 EMT 过程。从机制上讲,Circ_0008717 直接与靶向 GATA6 的 miR-326 结合。拯救实验表明,miR-326 逆转了 circ_0008717 敲低对 BC 细胞的抗癌作用。此外,miR-326 恢复抑制了 BC 细胞生长和转移,GATA6 过表达减弱了这些生长和转移。此外,我们还观察到 circ_0008717 可以通过海绵化 miR-326 来调节 GATA6 的表达。Circ_0008717 通过 miR-326/GATA6 轴促进乳腺癌的生长和转移,揭示了乳腺癌治疗的潜在治疗靶点。

更新日期:2022-08-25
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