Emerging research has indicated that circular RNAs (circRNAs), a novel class of noncoding RNAs, play a vital role in human tumorigenesis and progression. Our previous results suggested that hsa_circ_0006528 (circ_0006528), a circRNA with an unknown function, mediates adriamycin resistance in human breast cancer cells. However, the role of circ_0006528 in breast cancer progression remains unknown. Here, we investigated the probable involvement of circ_0006528 in breast cancer. We analyzed a cohort of 97 patients and found that circ_0006528 expression was significantly upregulated in human breast cancer tissues compared with that in adjacent nontumorous tissues and was significantly associated with advanced tumor-nodemetastasis (TNM) stage and poor prognosis. In addition, we found that in breast cancer cells, circ_0006528 could promote DNA synthesis and cell proliferation, invasion, and migration. Downregulating circ_0006528 induced G2 phase arrest and cell apoptosis. Further mechanistic studies revealed that circ_0006528 could sponge endogenous miR-7-5p and inhibit its activity. We also identified Raf1, which activates the MAPK/ERK signaling pathway, as a target of miR-7-5p and determined that circ_0006528 promotes breast cancer growth, invasion, and migration by promoting the expression of Raf1 and activates the MAPK/ERK pathway. Thus, this study provides the first evidence of the circ_0006528/miR-7-5p/Raf1/MEK/ERK regulatory network in the development of breast cancer and suggests that circ_0006528 is a potential therapeutic target and prognostic predictor for breast cancer.breast cancer, hsa_circ_0006528, invasion, migration, miR-7-5p, proliferation
| INTRODUCTIONBreast cancer is the most prevalent cancer in women worldwide and represents a serious public health problem. One complication in the clinical management of breast cancer is the tendency of malignant cells to shed into the circulation during the early stages of tumor development, 1,2 causing the formation of metastatic foci, a phenomenon that directly contributes to approximately 90% of breast cancerrelated mortality. 3,4 The precise genetic and epigenetic mechanisms that regulate the formation and malignant progression of tumors remain unclear and require further study. Therefore, it is essential to Danfeng Gao, Xiaowei Qi, and Xiufen Zhang contributed equally to this work.
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