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Circular RNA hsa_circ_0068033 inhibits proliferation and invasion of breast cancer cells through sponging miR-659

biorxiv(2019)

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摘要
Recently, dysregulated circular RNAs (circRNAs) have been associated with the progression of numerous malignant tumors. However, the mechanism through which circRNAs participate in breast cancer (BC) remains unclear. This study was designed to illustrate the role of hsa\_circ\_0068033 in BC. A series of functional experiments were conducted to assess the function of hsa\_circ\_0068033 in the development of BC and the underlying mechanisms. The results suggested that the expression of hsa\_circ\_0068033 was downregulated in BC tissues, and markedly correlated with tumor size ( P =0.021) and the Tumor, Node, and Metastasis stage ( P =0.023). Receiver operating characteristic analysis showed that hsa\_circ\_0068033 testing yielded an area under the curve value of 0.8480 in discriminating BC from non-tumor controls. Functionally, overexpression of hsa\_circ\_0068033 could inhibit the growth, clone formation, invasion, and migration of MCF-7 and MDA-MB-231 cells, while activating the intrinsic apoptotic pathway to induce apoptosis. The xenograft experiment revealed that exogenous hsa\_circ\_0068033 is able to reduce the tumorigenic ability of MDA-MB-231 cells in nude mice. Rescue assays further proved that hsa\_circ\_0068033 exerts biological functions by sponging miR-659. This study revealed for the first time that hsa\_circ\_0068033 acts as a tumor suppressor gene in BC, and the hsa\_circ\_0068033/miR-659 axis participates in the progression of BC.
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