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环状 RNA hsa_circ_0061825(circ-TFF1)通过靶向 miR-326/TFF1 信号通路促进乳腺癌进展。

Circular RNA hsa_circ_0061825 (circ-TFF1) contributes to breast cancer progression through targeting miR-326/TFF1 signalling.

机构信息

Minhang Hospital, Fudan University, Shanghai, China.

出版信息

Cell Prolif. 2020 Feb;53(2):e12720. doi: 10.1111/cpr.12720. Epub 2020 Jan 21.

Abstract

OBJECTIVES

Circular RNAs (circRNAs) are RNA transcripts that belong to non-coding RNAs (ncRNAs), whose implication in human cancers has been recently demonstrated. However, the specific role of multiple circRNAs in breast cancer remains unidentified.

MATERIALS AND METHODS

Microarray analysis and bioinformatics analysis were applied to select circRNA and miRNA, respectively. The loop structure of circ-TFF1 was confirmed using RNase R treatment, divergent primer PCR and Sanger sequencing. qRT-PCR and Western blot were employed for gene expressions. In vitro and in vivo experiments were conducted to assess the function of circ-TFF1 in biological processes in breast cancer cells. FISH and subcellular separation indicated circ-TFF1 cellular distribution. Luciferase reporter and RIP assays and Pearson's correlation analysis were performed to evaluate relationships between genes.

RESULTS

Circ-TFF1 and TFF1 were both upregulated and positively associated with each other in breast cancer. Knockdown of circ-TFF1 hindered breast cancer cell proliferation, migration, invasion and EMT in vitro and controlled tumour growth in vivo. Circ-TFF1 acted as a ceRNA of TFF1 by sponging miR-326, and its contribution to breast cancer progression was mediated by miR-326/TFF1 axis.

CONCLUSIONS

Circ-TFF1 is a facilitator in breast cancer relying on TFF1 by absorbing miR-326, providing a novel promising target for BC treatment.

摘要

目的

环状 RNA(circRNAs)属于非编码 RNA(ncRNAs)的 RNA 转录物,其在人类癌症中的作用最近已经得到证实。然而,多种 circRNAs 在乳腺癌中的具体作用仍未确定。

材料与方法

应用微阵列分析和生物信息学分析分别选择 circRNA 和 miRNA。用 RNase R 处理、发散引物 PCR 和 Sanger 测序来验证 circ-TFF1 的环结构。采用 qRT-PCR 和 Western blot 检测基因表达。在乳腺癌细胞中进行体外和体内实验,评估 circ-TFF1 在生物学过程中的功能。FISH 和亚细胞分离表明 circ-TFF1 的细胞分布。进行荧光素酶报告和 RIP 测定以及 Pearson 相关性分析来评估基因之间的关系。

结果

circ-TFF1 和 TFF1 在乳腺癌中均上调,并呈正相关。circ-TFF1 敲低可抑制乳腺癌细胞的体外增殖、迁移、侵袭和 EMT,并可控制体内肿瘤生长。circ-TFF1 通过海绵吸附 miR-326 作为 TFF1 的 ceRNA,其对乳腺癌进展的贡献由 miR-326/TFF1 轴介导。

结论

circ-TFF1 是乳腺癌的促进因子,通过吸收 miR-326 依赖 TFF1 发挥作用,为 BC 治疗提供了一个新的有前途的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e03e/7048212/c648a1aa872c/CPR-53-e12720-g001.jpg

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