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Circ_ZFR 通过作为 miR-223-3p 的海绵吸附体来影响 FABP7 表达,从而调控乳腺癌的进展。

Circ_ZFR affects FABP7 expression to regulate breast cancer progression by acting as a sponge for miR-223-3p.

机构信息

Department of Oncology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan, China.

Department of General Surgery, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan, China.

出版信息

Thorac Cancer. 2022 May;13(9):1369-1380. doi: 10.1111/1759-7714.14401. Epub 2022 Mar 30.

Abstract

BACKGROUND

Breast cancer (BC) is a common malignancy in women. Circular RNAs (circRNAs) have been reported to play a key role in the development of BC; however, the effect of circular RNA zinc finger RNA binding protein (circ_ZFR) in BC is unknown.

METHODS

Abundances of circ_ZFR, fatty acid binding protein 7 (FABP7), and microRNA-223-3p (miR-223-3p) were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The circular structure of circ_ZFR was validated by RNase R treatment. Cell proliferation, migration, invasion, and apoptosis were assessed by colony formation, cell counting kit-8, Transwell, flow cytometry assays, respectively. All protein levels were determined by Western blot. Dual-luciferase reporter assay was used to confirm the relationship between miR-223-3p and circ_ZFR or FABP7. A xenograft model was established to understand the effect of circ_ZFR on BC cell growth in vivo.

RESULTS

The expression levels of circ_ZFR and FABP7 were higher in BC tissues and cell lines, whereas miR-223-3p expression was lower. Knockdown of circ_ZFR or FABP7 in BC cells reduced proliferation, migration, invasion, and epithelial mesenchymal transition (EMT), and induced apoptosis in vitro, whereas the opposite effects were observed in circ_ZFR-overexpressed cells. Furthermore, circ_ZFR might act as a sponge for miR-223-3p to regulate FABP7 expression, thereby promoting the progression of BC cells in vitro and in vivo.

CONCLUSION

Circ_ZFR might act as a miRNA sponge for miR-223-3p to regulate FABP7, thereby promoting proliferation, migration, invasion, and EMT of BC cells, and inhibiting cell apoptosis.

摘要

背景

乳腺癌(BC)是女性常见的恶性肿瘤。环状 RNA(circRNA)已被报道在 BC 的发展中发挥关键作用;然而,环状 RNA 锌指 RNA 结合蛋白(circ_ZFR)在 BC 中的作用尚不清楚。

方法

通过实时定量聚合酶链反应(qRT-PCR)测量 circ_ZFR、脂肪酸结合蛋白 7(FABP7)和 microRNA-223-3p(miR-223-3p)的丰度。用 RNase R 处理验证 circ_ZFR 的环状结构。通过集落形成、细胞计数试剂盒-8、Transwell、流式细胞术分别评估细胞增殖、迁移、侵袭和凋亡。通过 Western blot 测定所有蛋白水平。双荧光素酶报告实验用于证实 miR-223-3p 与 circ_ZFR 或 FABP7 之间的关系。建立异种移植模型以了解 circ_ZFR 对体内 BC 细胞生长的影响。

结果

BC 组织和细胞系中 circ_ZFR 和 FABP7 的表达水平较高,而 miR-223-3p 的表达水平较低。BC 细胞中 circ_ZFR 或 FABP7 的敲低减少了体外增殖、迁移、侵袭和上皮间质转化(EMT),并诱导了细胞凋亡,而在 circ_ZFR 过表达的细胞中则观察到相反的效果。此外,circ_ZFR 可能作为 miR-223-3p 的海绵体调节 FABP7 的表达,从而促进 BC 细胞在体外和体内的进展。

结论

circ_ZFR 可能作为 miR-223-3p 的海绵体调节 FABP7,从而促进 BC 细胞的增殖、迁移、侵袭和 EMT,并抑制细胞凋亡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be42/9058297/8d0cd7e1419d/TCA-13-1369-g003.jpg

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