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环状 RNA circ_0103552 通过海绵吸附 miR-1236 预测不良预后并促进乳腺癌细胞增殖和侵袭。

Circular RNA circ_0103552 forecasts dismal prognosis and promotes breast cancer cell proliferation and invasion by sponging miR-1236.

机构信息

Department of Oncology, The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar, China.

Department of Foreign Languages, Dalian Jiaotong University, Dalian, China.

出版信息

J Cell Biochem. 2019 Sep;120(9):15553-15560. doi: 10.1002/jcb.28822. Epub 2019 May 5.

Abstract

Breast cancer (BC) is a fatal malignancy, which has a high incidence and mortality across the world. Circular RNAs (circRNAs) have crucial roles in tumor initiation and progression. In this project, a newly found circRNA, circ_0103552 was explored. Quantitative real-time polymerase chain reaction was applied to measure its expression in the patients' tissue specimens and cells. In addition, Fisher's exact test, Kaplan-Meier curves and Cox regression model were conducted to discover the clinical significance of circ_0103552. Cell viability, clone-forming ability, apoptosis, and metastatic properties of BC cells were evaluated by gain/loss-of-function assays. Dual luciferase reporter assay was applied to illuminate its mechanisms. As data indicated, circ_0103552 was significantly elevated in BC tissue samples and cells. In addition, its expression correlates with clinical severity and dismal prognosis. Furthermore, circ_0103552 could facilitate cell growth, clone-forming ability, migration and invasion, and decrease apoptotic cells. For the mechanism exploration, circ_0103552 could directly sponge miR-1236 to execute oncogenic activities in BC cells. In summary, this study provides a novel circRNA in tumorigeneis and progression of BC and may help to develop effective therapeutic target for this devastating disease.

摘要

乳腺癌(BC)是一种致命的恶性肿瘤,在全球范围内发病率和死亡率都很高。环状 RNA(circRNA)在肿瘤的发生和发展中起着至关重要的作用。在这个项目中,研究了一种新发现的 circRNA,circ_0103552。应用实时定量聚合酶链反应(qRT-PCR)测量其在患者组织标本和细胞中的表达。此外,还进行了 Fisher 确切检验、Kaplan-Meier 曲线和 Cox 回归模型分析,以发现 circ_0103552 的临床意义。通过增益/缺失功能测定评估了 BC 细胞的细胞活力、克隆形成能力、细胞凋亡和转移特性。应用双荧光素酶报告基因检测来阐明其机制。结果表明,circ_0103552 在 BC 组织标本和细胞中明显上调。此外,其表达与临床严重程度和预后不良相关。此外,circ_0103552 可以促进细胞生长、克隆形成能力、迁移和侵袭,并减少凋亡细胞。为了探索其机制,circ_0103552 可以直接吸附 miR-1236 来执行 BC 细胞中的致癌活性。综上所述,本研究提供了一种新的环状 RNA 在乳腺癌发生和进展中的作用机制,可能有助于为这种毁灭性疾病开发有效的治疗靶点。

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