Abstract
Growing evidence suggests that circRNAs exert a critical role in tumorigenesis and cancer progression. To date, the molecular mechanisms underlying circRNAs in triple-negative breast cancer (TNBC) are still poorly known. Here, circRNA expression profile was investigated by RNA sequencing in TNBC tissues and matched para-carcinoma tissues. We found that circIFI30 was significantly up-regulated in TNBC tissues and cells using quantitative real-time PCR and in situ hybridization. High circIFI30 expression was positively correlated with clinical TNM stage, pathological grade and poor prognosis of TNBC patients. Functionally, a series of in vivo and in vitro experiments showed that knockdown of circIFI30 could markedly inhibit TNBC cell proliferation, migration, invasion and cell cycle progression, induce apoptosis as well as suppress tumorigenesis and metastasis. Up-regulation of circIFI30 exerted an opposite effect. Mechanistically, we demonstrated that circIFI30 might act as a competing endogenous RNA (ceRNA) of miR-520b-3p to abolish the suppressive effect on target gene CD44 by fluorescent in situ hybridization (FISH), dual luciferase reporter assay, RNA immunoprecipitation and RNA pull-down assays. Therefore, our work uncovers the mechanism by which circIFI30 could promote TNBC progression through circIFI30/miR-520b-3p/CD44 axis and circIFI30 could be a novel diagnostic/prognostic marker and therapeutic target for TNBC patients.
Highlights
Breast cancer is the most common female cancer, new cases and deaths for breast cancer were 2,088,849 and 626,679, accounting for almost 1 in 4 cancer cases among women in 2018 around the world according to Global Cancer Statistics [1]
The result showed that 354 circRNAs were significantly differentially expressed in Triple-negative breast cancer (TNBC) tissues compared with paired adjacent normal tissues, of which 47 were upregulated and 307 were downregulated (Figure 1A)
We discovered that circIFI30 was one of the most significantly up-regulated circRNAs in TNBC
Summary
Breast cancer is the most common female cancer, new cases and deaths for breast cancer were 2,088,849 and 626,679, accounting for almost 1 in 4 cancer cases among women in 2018 around the world according to Global Cancer Statistics [1]. Despite the early detection and efficient systemic treatment, breast cancer is the leading cause of cancer death in over 100 countries. Triple-negative breast cancer (TNBC) is a breast cancer subtype with negative expressions of estrogen receptor (ER), progesterone receptors (PR) and human epidermal growth factor receptor 2 (HER2). The median survival time of patients with metastatic TNBC was only 13.3 months [2]. TNBC patients lack effective endocrine therapy and anti-HER2 www.aging-us.com targeted therapy because of no expression of ER, PR and HER2. Chemotherapy remains the main treatment for TNBC [3]. Investigating the molecular mechanisms underlying tumorigenesis and development of TNBC as well as finding the effective potential target are of great significance for improving the survival and prognosis for TNBC patients
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