Hsa_circ_0002496 通过 miR-433-3p/YWHAZ 级联促进乳腺癌细胞的生长、血管生成和干性。

Hsa_circ_0002496 promotes the growth, angiogenesis, and stemness of breast cancer cells via miR-433-3p/YWHAZ cascade.

机构信息

Department of Breast Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.

Department of Tumor Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.

出版信息

Thorac Cancer. 2023 Jun;14(18):1732-1741. doi: 10.1111/1759-7714.14918. Epub 2023 May 9.

DOI:10.1111/1759-7714.14918

PMID:37160403

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10290916/

Abstract

BACKGROUND

Breast cancer (BC) has been studied more and more in modern medicine. Circ_0002496 has established a critical role in BC. MiR-433-3p can exert important activity in cancer. YWHAZ can participate in BC development, but the targeting relationship among the three variables and its influence on the related process of BC are not clear.

METHODS

RT-qPCR was used to analyze circ_0002496, miR-433-3p, and YWHAZ expression. Immunoblotting was used to analyze YWHAZ, Bax, Bcl-2, and PI3K/AKT-related proteins. RNase R assay was used to verify the ring structure of circ_0002496. Cell phenotypes were tested by Cell Counting Kit 8, EdU, sphere formation, tube formation, and flow cytometry assays.

RESULTS

Circ_0002496 was enhanced and MiR-433-3p was downregulated in BC, while the expression of YWHAZ was higher in BC. Circ_0002496 targeted miR-433-3p and miR-433-3p targeted YWHAZ in BC cells. Depletion of circ_0002496 influenced the BC process, but miR-433-3p inhibitor reversed the impact of si-circ_0002496 on the BC process. Re-expression of YWHAZ weakened the influence of miR-433-3p on the BC process. Depletion of circ_0002496 could astrict tumor growth in vivo. Moreover, the circ_0002496/miR-433-3p/YWHAZ axis mediated the activation of the PI3K/AKT signaling pathway.

CONCLUSION

Circ_0002496 participated in the malignant procession of BC by miR-433-3p/YWHAZ regulation cascade.

摘要

背景

乳腺癌（BC）在现代医学中受到越来越多的研究。Circ_0002496 在 BC 中建立了关键作用。miR-433-3p 可以在癌症中发挥重要活性。YWHAZ 可以参与 BC 的发展，但这三个变量之间的靶向关系及其对 BC 相关过程的影响尚不清楚。

方法

使用 RT-qPCR 分析 circ_0002496、miR-433-3p 和 YWHAZ 的表达。使用免疫印迹分析 YWHAZ、Bax、Bcl-2 和 PI3K/AKT 相关蛋白。使用 RNase R 测定验证 circ_0002496 的环状结构。通过细胞计数试剂盒 8、EdU、球体形成、管形成和流式细胞术测定测试细胞表型。

结果

Circ_0002496 在 BC 中增强，miR-433-3p 下调，而 YWHAZ 在 BC 中的表达更高。Circ_0002496 在 BC 细胞中靶向 miR-433-3p，而 miR-433-3p 靶向 YWHAZ。Circ_0002496 的耗竭影响 BC 过程，但 miR-433-3p 抑制剂逆转了 si-circ_0002496 对 BC 过程的影响。YWHAZ 的再表达削弱了 miR-433-3p 对 BC 过程的影响。Circ_0002496 的耗竭可以限制体内肿瘤的生长。此外，circ_0002496/miR-433-3p/YWHAZ 轴介导了 PI3K/AKT 信号通路的激活。