Identification and Validation of circDOCK1/miR-138-5p/GRB7 Axis for Promoting Breast Cancer Progression.

IF 3.3 4区 医学 Q2 ONCOLOGY
Breast Cancer : Targets and Therapy Pub Date : 2024-11-26 eCollection Date: 2024-01-01 DOI:10.2147/BCTT.S495517
Yan Zhang, Mei Yang, Yiping Wang, Junhao Zhao, Pei Yao Lee, Yuhua Ma, Shaohua Qu
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引用次数: 0

Abstract

Background: Non-coding RNAs have received increasing attention in human tumors, with RNA interaction networks playing important roles in breast cancer. This study aims to explore novel circular RNAs and their mechanisms of biological function in breast cancer.

Methods: Six HER2-positive breast cancer tissues and paired normal tissues were obtained for the whole transcriptome RNA sequencing. Differentially expressed (DE) circRNAs, miRNAs and mRNAs were identified and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of DERNAs were performed. DECircRNAs- DEmiRNAs- DEmRNAs networks were constructed and further verified by bioinformatics database analyses, luciferase assays and RIP assays. The expression level of circDOCK1 in breast cancer specimens was measured using qRT-PCR. Functional rescue experiments were conducted to explore the role of circDOCK1/miR-138-5p/GRB7 axis in breast cancer cells. The correlation of circDOCK1 expression and clinicopathologic features of 102 HER2 positive breast cancer patients was analyzed.

Results: A total of 6960 DEmRNAs, 133 DE miRNAs and 1691 DE circRNAs were identified from HER2-positive breast cancer tissues and paracancerous tissues. Enrichment Analysis showed that the differential mRNAs were associated with cell division in biological processes and cell cycle and signaling pathways. GO and KEGG analysis demonstrated that DE circRNAs were mainly enriched in double-strand break repair, positive regulation of transcription by RNA polymerase II, nucleoplasma, nucleus, chromatin binding and protein binding. Forty networks of competing endogenous RNAs (ceRNAs) were constructed and circDOCK1/miR-138-5p/GRB7 axis was verified. Functional experiments revealed that the axis promotes migration and invasion of breast cancer cells. CircDOCK1 expression was elevated in breast cancer patients and correlated with adverse clinicopathologic parameters. Patients with high circDOCK1 level had poor outcomes.

Conclusion: A novel circDOCK1/miR-138-5p/GRB7 axis promotes HER2 positive breast cancer metastasis and progression, providing a potential therapeutic target in the treatment of breast cancer.

circDOCK1/miR-138-5p/GRB7轴促进乳腺癌进展的鉴定和验证
背景:非编码RNA在人类肿瘤中受到越来越多的关注,RNA相互作用网络在乳腺癌中发挥着重要作用。本研究旨在探索新型环状rna及其在乳腺癌中的生物学功能机制。方法:选取6例her2阳性乳腺癌组织及配对正常组织进行全转录组RNA测序。鉴定差异表达(DE)环状rna、mirna和mrna,并对DERNAs进行基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析。构建DECircRNAs- DEmiRNAs- demmrnas网络,并通过生物信息学数据库分析、荧光素酶测定和RIP测定进一步验证。采用qRT-PCR检测乳腺癌标本中circDOCK1的表达水平。通过功能挽救实验探讨circDOCK1/miR-138-5p/GRB7轴在乳腺癌细胞中的作用。分析102例HER2阳性乳腺癌患者circDOCK1表达与临床病理特征的相关性。结果:从her2阳性乳腺癌组织和癌旁组织中共鉴定出6960个demrna、133个DE mirna和1691个DE circrna。富集分析表明,这些差异mrna与细胞分裂的生物学过程、细胞周期和信号通路有关。GO和KEGG分析表明,DE circRNAs主要富集于双链断裂修复、RNA聚合酶II转录正调控、核浆、细胞核、染色质结合和蛋白质结合。构建了40个竞争内源性rna (ceRNAs)网络,并验证了circDOCK1/miR-138-5p/GRB7轴。功能实验显示,该轴促进乳腺癌细胞的迁移和侵袭。CircDOCK1在乳腺癌患者中表达升高,并与不良临床病理参数相关。circDOCK1水平高的患者预后较差。结论:一个新的circDOCK1/miR-138-5p/GRB7轴促进HER2阳性乳腺癌的转移和进展,为乳腺癌的治疗提供了一个潜在的治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
4.10
自引率
0.00%
发文量
40
审稿时长
16 weeks
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