OncoTargets and Therapy (Aug 2019)
Hsa_circ_0008945 promoted breast cancer progression by targeting miR-338-3p
Abstract
Li Zhang, Fengping DingDepartment of Pathology, People’s Hospital of Xinchang County, Xinchang Affiliated Hospital of Wenzhou Medical University, Xinchang, Zhejiang, People’s Republic of ChinaCorrespondence: Li ZhangDepartment of Pathology, People’s Hospital of Xinchang County, Xinchang Affiliated Hospital of Wenzhou Medical University, 117 Gushan Middle Road, Nanming Street, Xinchang 312500, People’s Republic of ChinaTel +86 1 895 756 8155Email [email protected]: To detect the expression and function of circ_0008945 in breast cancer (BC) and to explore its potential molecular mechanisms in BC tumorigenesis.Materials and methods: We measured expression levels of circ_0008945, miR-338-3p and homeobox A3 (HOXA3) in BC tissue specimens and cells using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). We examined the effects of all three genes on BC cell proliferation using Cell Counting Kit-8 (CCK-8) and colony formation assays. We also performed a Transwell assay to assess the migratory and invasive ability of treated BC cells. BC cell apoptosis was assessed using flow cytometric (FCM) analysis; interaction between miR-338-3p and circ_0008945 or HOXA3 was verified by dual-luciferase reporter assay as well as by ribonucleic-acid (RNA) pulldown. Finally, we used an in vivo tumor growth assay to assess the role of circ_0008945 overexpression in BC tumor growth.Results: We found that circ_0008945 expression was significantly increased in both BC tissue specimens and cells. This increase was correlated with poor prognosis in BC patients. Knockdown of circ_0008945 inhibited BC cell proliferation, migration and invasion while promoting BC cell apoptosis in vitro. Overexpression of circ_0008945 remarkably promoted BC tumor growth in vivo. Mechanistically, circ_0008945 acted as a miRNA sponge for miR-338-3p and inhibited its expression in BC cells. Moreover, miR-338-3p targeted and inhibited HOXA3.Conclusion: We found that circ_0008945 acted as a BC oncogene by physically binding miR-338-3p, which further targeted and regulated HOXA3.Keywords: apoptosis, breast cancer, circ_0008945, miR-338-3p, proliferation
