circRNA_0025202 Regulates Tamoxifen Sensitivity and Tumor Progression via Regulating the miR-182-5p/FOXO3a Axis in Breast Cancer

Abstract

Tamoxifen is the most commonly used endocrine therapy for patients with hormone receptor (HR)-positive breast cancer. Despite its initial therapeutic efficacy, many patients eventually develop drug resistance, which remains a serious clinical challenge. To investigate roles of circular RNAs (circRNAs) in tamoxifen resistance, a tamoxifen-resistant MCF-7 cell line was established and screened for its circRNA expression profile by RNA sequencing. hsa_circ_0025202, a circRNA that was significantly downregulated, was selected for further investigation. Using a large cohort of clinical specimens, we found that hsa_circ_0025202 exhibited low expression in cancer tissues and was negatively correlated with lymphatic metastasis and histological grade. Gainand loss-of-function assays indicated that hsa_circ_0025202 could inhibit cell proliferation, colony formation, and migration and increase cell apoptosis and sensitivity to tamoxifen. Bioinformatics and luciferase reporter assays verified that hsa_circ_0025202 could act as a miRNA sponge for miR-182-5p and further regulate the expression and activity of FOXO3a. Functional studies revealed that tumor inhibition and tamoxifen sensitization effects of hsa_circ_0025202 were achieved via the miR-182-5p/FOXO3a axis. Moreover, in vivo experiments confirmed that hsa_circ_0025202 could suppress tumor growth and enhance tamoxifen efficacy. Taken together, hsa_circ_ 0025202 served an anti-oncogenic role in HR-positive breast cancer, and it could be exploited as a novel marker for tamoxifen-resistant breast cancer.

Large-scale quantitative genomics analyzes the circRNA expression profile and identifies the key circRNA in regulating cell proliferation during the proliferation phase of rat LR

“…In addition, miR-378 expression declined, accompanied by remarkably increased expression of its target ornithine decarboxylase 1 (ODC1) from 0 to 18 h after PH [36], and ODC1 was found that involved in positive regulation of cell population proliferation [37]. Our results were consistent with those reports by others about the expression of ceRNAs was negatively correlated [38], showing that circ_03848 might target these miRNAs and affect downstream gene expression in regulating cell proliferation. Additionally, circ_08236 exhibited an upregulated pattern at 36 h after PH and predicted to target rno-miR-143-5p in this paper.…”

Construction and Investigation of circRNA-miRNA-mRNA ceRNA regulatory network in breast cancer

“…Increasing study has indicated the vital role circRNAs play in tumor progression, and because of the relative tolerance of these circRNAs to exonuclease, it may be a better biomarker to judge the prognosis of patients [17]. Additionally, more and more circRNAs, for instance hsa_circ_0025202 [18], circAGFG1 [12], circGFRA1 [19], circ_ANKS1B [20], have been pointed out to play important roles in tumorigenesis, chemoresistance, apoptosis or metasta sis of BC. Nevertheless, many of the functions of circRNAs in BC remain to be explored.…”

Hsa_circ_0005273 regulates YAP1-Hippo signaling pathway by targeting miR-200a-3p to promote breast cancer progression.

“…More importantly, studies focused on the relationship between BC and circRNAs also achieved attention. For instance,circRNA_0025202 regulates tamoxifen sensitivity and tumor progression via regulating the miR-182-5p in Breast Cancer [31]. CircTADA2As suppress BC progression and metastasis via targeting miR-203a-3p [32].…”