Purpose: 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.
Methods: We detected the expression levels of hsa_circ_0068033 in BC tissues using quantitative real-time PCR (qRT-PCR) and in situ hybridization (ISH). A series of functional experiments were conducted to assess the function of hsa_circ_0068033 in BC development and the underlying mechanisms.
Results: The results suggested that the expression of hsa_circ_0068033 was downregulated in BC tissues, and its expression was 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, in-vitro experiments demonstrated that overexpression of hsa_circ_0068033 could inhibit the growths, 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 evidently 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.
Conclusion: Collectively, 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.
Keywords: circular RNA, hsa_circ_0068033, breast cancer, miR-659, sponge