OncoTargets and Therapy (Jun 2020)
Circular RNA 0001073 Attenuates Malignant Biological Behaviours in Breast Cancer Cell and Is Delivered by Nanoparticles to Inhibit Mice Tumour Growth
Abstract
Ziying Yi,1,2 Yunhai Li,1,2 Yushen Wu,1 Beilei Zeng,1 Hongzhong Li,1,2 Guosheng Ren,1,2 Xiaoyi Wang2 1Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Guosheng Ren; Xiaoyi WangThe First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, People’s Republic of ChinaTel +86 023 8901 1477Fax +86 023 8901 2305Email [email protected]; [email protected]: Circular RNAs (circRNAs) are a special class of noncoding RNAs that are involved in gene regulation and compete with mRNA for miRNA binding sites. The roles of circRNAs in cancer, especially breast cancer (BC), are poorly understood.Materials and Methods: The expression levels of circRNA 0001073 (circ-1073) in BC cells (BCCs) and tissues and peritumoural tissues were detected by real-time quantitative reverse transcription-polymerase chain reaction. Kaplan–Meier analysis and receiver operating characteristic curves were used to evaluate relapse-free survival (RFS) and the diagnostic value of circ-1073 for BC, respectively. The biological functions of circ-1073 were determined by cell counting kit-8 assays, colony formation assays, flow cytometry, wound-healing assays, transwell assays, and xenograft model studies. RNA immunoprecipitation assays were conducted to identify the connection between circ-1073 and human antigen R (HuR).Results: Low circ-1073 expression was discovered in BCCs and BC tissues compared with normal mammary epithelial cells and peritumoural tissues, respectively. Circ-1073 downregulation was significantly associated with an unfavourable prognosis, including a shorter RFS, in BC patients. Circ-1073 is a valuable diagnostic biomarker for BC. Circ-1073 overexpression significantly inhibited BCC proliferation and induced apoptosis by increasing Cleaved Caspase-3/9 levels. Moreover, circ-1073 upregulation significantly suppressed cell mobility and epithelial–mesenchymal transition. Notably, xenograft tumour growth was inhibited by the intratumoural injection of nanoparticles containing the circ-1073 plasmid or by circ-1073 overexpression, and this inhibition was accompanied by HuR upregulation.Conclusion: Circ-1073 functions as a tumour suppressor in BC, suggesting its potential as a novel therapeutic target in BC.Keywords: circ-1073, breast cancer, apoptosis, metastasis, nanoparticles, HuR
