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环状结构特异性蛋白 42 在三阴性乳腺癌中下调,并与不良预后相关。

circUSP42 Is Downregulated in Triple-Negative Breast Cancer and Associated With Poor Prognosis.

机构信息

Department of General Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.

Department of Breast Surgery, Shanghai Changning Maternity and Infant Health Hospital, East China Normal University, Shanghai, China.

出版信息

Technol Cancer Res Treat. 2020 Jan-Dec;19:1533033820950827. doi: 10.1177/1533033820950827.

Abstract

We previously showed that microRNA-182 (miR-182) might promote cell proliferation and migration in triple-negative breast cancer (TNBC). This study aimed to investigate circular RNAs (circRNAs) that interact with miR-182 and play important roles in TNBC. Thirty patients with TNBC were enrolled. One pair of tumor and adjacent tissue samples (control) were submitted for circRNA sequencing to establish the expression profile of circRNAs. Concomitantly, circRNAs aberrantly expressed between TNBC and control groups were identified, and these differentially expressed circRNAs (DEcircRNAs) were subjected to Gene Ontology and KEGG pathway enrichment analyses, as well as prediction of interactions with miRNAs. The expression levels of 5 circRNAs interacting with miR-182 were validated using qRT-PCR. Associations between the expression of circUSP42 and clinicopathological features and prognosis were evaluated. A total of 825 upregulated and 1127 downregulated DEcircRNAs were identified between tumor and control groups. Upregulated DEcircRNAs were significantly involved in proteoglycans in cancer, and endocytosis. Downregulated DEcircRNAs were involved in the pathway of resistance to EGFR tyrosine kinase inhibitors. Prediction of circRNA-miRNA interactions showed that hsa_circ_0002032, chr6:131973682-132047340+, hsa_circ_0005982, hsa_circ_0007823 (circUSP42), and hsa_circ_0001777 might act as miRNA sponges for miR-182. qRT-PCR showed consistent results with circRNA sequencing data ( < 0.05). Downregulation of circUSP42 was significantly associated with lymph node metastasis ( = 0.005) and advanced clinical stage ( = 0.032). Furthermore, Kaplan-Meier plots showed that low expression of circUSP42 was closely associated with poor outcome (log-rank test, < 0.001). Our data suggested that dysregulation of circUSP42 might contribute to the development and progression of TNBC.

摘要

我们之前表明,微小 RNA-182(miR-182)可能促进三阴性乳腺癌(TNBC)中的细胞增殖和迁移。本研究旨在研究与 miR-182 相互作用并在 TNBC 中发挥重要作用的环状 RNA(circRNA)。纳入了 30 名 TNBC 患者。一对肿瘤和相邻组织样本(对照)用于 circRNA 测序,以建立 circRNA 的表达谱。同时,鉴定了 TNBC 与对照组之间差异表达的 circRNA(DEcircRNA),并对其进行了基因本体论和 KEGG 通路富集分析,以及与 miRNAs 相互作用的预测。使用 qRT-PCR 验证了与 miR-182 相互作用的 5 个 circRNA 的表达水平。评估了 circUSP42 的表达与临床病理特征和预后的关系。在肿瘤组和对照组之间共鉴定出 825 个上调和 1127 个下调的 DEcircRNA。上调的 DEcircRNA 显著参与癌症中的蛋白聚糖和内吞作用。下调的 DEcircRNA 参与 EGFR 酪氨酸激酶抑制剂耐药的途径。circRNA-miRNA 相互作用的预测表明,hsa_circ_0002032、chr6:131973682-132047340+、hsa_circ_0005982、hsa_circ_0007823(circUSP42)和 hsa_circ_0001777 可能作为 miR-182 的 miRNA 海绵。qRT-PCR 显示与 circRNA 测序数据一致的结果(<0.05)。circUSP42 的下调与淋巴结转移(=0.005)和临床晚期(=0.032)显著相关。此外,Kaplan-Meier 图表明 circUSP42 的低表达与不良预后密切相关(对数秩检验,<0.001)。我们的数据表明,circUSP42 的失调可能有助于 TNBC 的发展和进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00b9/7502800/3d2a747b8467/10.1177_1533033820950827-fig1.jpg

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