新型 circFKBP8/miR-432-5p/E2F7 级联在乳腺癌中作为一个调控网络发挥作用。

The novel circFKBP8/miR-432-5p/E2F7 cascade functions as a regulatory network in breast cancer.

机构信息

Department of Breast Surgery, Yichun People's Hospital & The Affiliated Yichun Hospital of Nanchang University, No.1061 Jinxiu avenue, Yiyang New District 336000, Yichun, Jiangxi, China.

出版信息

Hereditas. 2024 Aug 27;161(1):27. doi: 10.1186/s41065-024-00331-1.

DOI:10.1186/s41065-024-00331-1

PMID:39192374

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11348600/

Abstract

BACKGROUND

Circular RNAs (circRNAs) are capable of affecting breast cancer (BC) development. However, the role and underneath mechanism of circFKBP8 (also known as hsa_circ_0000915) in BC remain largely unknown.

METHODS

Expression analyses were performed using quantitative real-time polymerase chain reaction (qRT-PCR), western blot, and immunohistochemistry (IHC) assays. Effects on cell functional phenotypes were determined by assessing cell proliferation, migratory capacity, invasion, and stemness in vitro. The relationship between microRNA (miR)-432-5p and circFKBP8 or E2F transcription factor 7 (E2F7) was examined by RNA pull-down, dual-luciferase reporter, and RNA immunoprecipitation (RIP) assays. Xenograft assays were used to identify the function of circFKBP8 in vivo.

RESULTS

CircFKBP8 was presented at high levels in BC tissues and cells. High circFKBP8 expression was associated with worse overall survival in BC patients. CircFKBP8 suppression inhibited BC cell proliferation, migratory capacity, invasion and stemness in vitro. CircFKBP8 suppression blocked xenograft tumor growth in vivo. Mechanistically, circFKBP8 functioned as a miR-432-5p sponge to modulate E2F7 expression. CircFKBP8 modulated BC cell malignant behaviors by miR-432-5p, and miR-432-5p affected these cell phenotypes through E2F7.

CONCLUSION

Our observations prove that circFKBP8 promotes BC malignant phenotypes through the miR-432-5p/E2F7 cascade, offering a promising therapeutic and prognostic target for BC.

摘要

背景

环状 RNA（circRNAs）能够影响乳腺癌（BC）的发展。然而，circFKBP8（也称为 hsa_circ_0000915）在 BC 中的作用和潜在机制在很大程度上仍不清楚。

方法

使用实时定量聚合酶链反应（qRT-PCR）、western blot 和免疫组织化学（IHC）检测进行表达分析。通过体外评估细胞增殖、迁移能力、侵袭和干性来确定对细胞功能表型的影响。通过 RNA 下拉、双荧光素酶报告基因和 RNA 免疫沉淀（RIP）检测来研究 microRNA（miR）-432-5p 与 circFKBP8 或 E2F 转录因子 7（E2F7）之间的关系。使用异种移植实验来鉴定 circFKBP8 在体内的功能。

结果

circFKBP8 在 BC 组织和细胞中呈高表达。circFKBP8 高表达与 BC 患者的总生存率较差相关。circFKBP8 抑制可抑制 BC 细胞的体外增殖、迁移能力、侵袭和干性。circFKBP8 抑制可阻止体内异种移植肿瘤的生长。机制上，circFKBP8 作为 miR-432-5p 的海绵体来调节 E2F7 的表达。circFKBP8 通过 miR-432-5p 调节 BC 细胞恶性行为，而 miR-432-5p 通过 E2F7 影响这些细胞表型。