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环状 ACAP2 通过靶向 miR-29a/b-3p-COL5A1 轴促进乳腺癌的增殖和转移。

CircACAP2 promotes breast cancer proliferation and metastasis by targeting miR-29a/b-3p-COL5A1 axis.

机构信息

Department of Thyroid and Breast Surgery, Zhoukou Central Hospital, Zhoukou City, 466000, Henan Province, PR China.

Department of Thyroid and Breast Surgery, Zhoukou Central Hospital, Zhoukou City, 466000, Henan Province, PR China.

出版信息

Life Sci. 2020 Mar 1;244:117179. doi: 10.1016/j.lfs.2019.117179. Epub 2019 Dec 19.

DOI:10.1016/j.lfs.2019.117179
PMID:31863774
Abstract

BACKGROUND

Breast cancer is the most common cancer occurred in female around the world. The occurrence percentage of breast cancer among female who was over 50 years old is >80%. These factors may induce the chance of morbidity, including heavy drinking for a long term, smoking and postmenopausal obesity. Treatment of adjuvant chemotherapeutic and hormonal agents is mostly applied nowadays, which does contribute to the improvement of breast cancer, yet it is still an intractable disease for the side effects it brings. Emerging evidence has proved circular RNAs are involved in gene expression and modulation of biological behaviors. However, the mechanism and functions of circRNA ACAP2 (circACAP2) with respect to breast cancer remain unexplored.

METHODS

qRT-PCR analysis was used to detect relevant expression. Bioinformatics analysis was applied to seek miRNAs which might have binding sites with circACAP2 and miR-29a/b-3p. Functional experiments including CCK-8, colony formation assay and flow cytometry assay detected gene function role in breast cancer cells. RIP, RNA pull down and Luciferase reporter assays were carried out to verify binding sites among circACAP2, miR-29a/b-3p and COL5A1.

RESULTS

CircACAP2 expression was prominently elevated in tumorous tissues. Functionally and mechanistically, circACAP2 promoted breast cancer proliferation and motility by sponging miR-29a/b-3p and modulating COL5A1.

CONCLUSION

Elevated expression of circACAP2 in breast cancer tissues leads to malignant phenotype upon cancerous cells. CircACAP2-miR-29a/b-3p-COL5A1 axis leads to breast cancer tumorigenesis and could hopefully be a novel method for diagnosis and treatment for breast cancer.

摘要

背景

乳腺癌是全世界女性中最常见的癌症。50 岁以上女性乳腺癌的发病率>80%。这些因素可能会增加发病的机会,包括长期大量饮酒、吸烟和绝经后肥胖。目前主要应用辅助化疗和激素治疗药物,这有助于改善乳腺癌,但它仍然是一种难以治愈的疾病,因为它会带来副作用。新出现的证据证明环状 RNA 参与基因表达和生物行为的调节。然而,circRNA ACAP2(circACAP2)与乳腺癌的关系及其机制和功能仍未被探索。

方法

qRT-PCR 分析用于检测相关表达。生物信息学分析用于寻找可能与 circACAP2 结合的 miRNA。包括 CCK-8、集落形成实验和流式细胞术实验在内的功能实验检测基因在乳腺癌细胞中的功能作用。RIP、RNA 下拉和荧光素酶报告实验用于验证 circACAP2、miR-29a/b-3p 和 COL5A1 之间的结合位点。

结果

circACAP2 在肿瘤组织中表达明显升高。在功能和机制上,circACAP2 通过海绵吸附 miR-29a/b-3p 和调节 COL5A1 促进乳腺癌的增殖和迁移。

结论

乳腺癌组织中 circACAP2 的高表达导致癌细胞发生恶性表型。circACAP2-miR-29a/b-3p-COL5A1 轴导致乳腺癌的发生,有望成为诊断和治疗乳腺癌的新方法。

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