CircRNA circ_0075796 is downregulated in breast cancer and suppresses cell proliferation, migration and invasion

Abstract Background Emerging evidence shows that circular RNAs (circRNAs) play crucial parts in tumorigenesis and progression. In this work, the expression, clinical significance, function and potential mechanism of circ_0075796 in breast cancer were explored. Methods The expression of circ_0075796 in 189 pairs of breast cancer tissues and adjacent normal tissues was detected by quantitative real-time PCR (qRT-PCR). Cell Counting Kit-8 (CCK-8) assay, methyl thiazolyl tetrazolium (MTT) assay and colony formation assay were conducted for cell proliferation. Transwell assay and wound healing assay were used for cell migration and invasion. Flow cytometry analysis was adopted for cell cycle and cell apoptosis. The cellular localization of circ_0075796 was determined by fluorescence in situ hybridization (FISH). The circ_0075796/miR-452-3p/SAMD5 axis was screened out by bioinformatics analysis and verified by qRT-PCR. Methylated RNA Immunoprecipitation (MeRIP) was used to detect the N6-methyladenosine (m6A) modification levels of circ_0075796. QRT-PCR was used to detect the expression of RNA binding protein Quaking (QKI) in breast cancer tissues and adjacent normal tissues. Results circ_0075796 was downregulated in breast cancer tissues compared with adjacent normal tissues. In addition, circ_0075796 showed satisfactory diagnostic value to discriminate breast cancer and normal controls. Downregulated circ_0075796 expression was correlated with lymph node metastasis, HER2 expression, larger tumor size, high Ki-67 expression, advanced histological grade, aggressive molecular subtypes and advanced clinical stages. Overexpression of circ_0075796 inhibited cell proliferation, migration and invasion in vitro. FISH showed that circ_0075796 was localized in the cytoplasm and nucleus of breast cancer cells. Bioinformatics analysis and qRT-PCR revealed the potential circ_0075796/miR-452-3p/SAMD5 axis. Moreover, circ_0075796 showed lower m6A modification levels in breast cancer tissues compared to adjacent normal tissues. QKI was predicted to contain binding sites of circ_0075796 and was downregulated in breast cancer tissues compared to adjacent normal controls. Conclusions circ_0075796 was downregulated in breast cancer compared to normal controls, and showed potential diagnostic value for breast cancer. Downregulation of circ_0075796 was correlated with aggressive clinical features of breast cancer and overexpression of circ_0075796 inhibited the progression of breast cancer in vitro, indicating that circ_0075796 may be related to tumorigenesis and development of breast cancer.