Abstract
Introduction: The role and underlying mechanisms of miR-27b-3p in triple-negative breast cancer (TNBC) remains unclear.Methods: miR-27b-3p expression level was evaluated in 99 TNBC patients with a median follow-up time of 133 months. The biological functions of miR-27b-3p by targeting PPARG were assessed by luciferase reporter assay, CCK-8 assay, Transwell assay, wound healing assay, western blot analysis and xenograft models.Results: High level of miR-27b-3p expression was found to confer poor prognosis in TNBC patients. MiR-27b-3p overexpression increased TNBC cell proliferation, migration, invasion, and metastasis. Our data suggested peroxisome proliferator-activated receptor gamma (PPARG) was a target of miR-27b-3p. The capacity of miR-27b-3p to induce TNBC progression and metastasis depended on its inhibition of the PPARG expression. Furthermore, restoring PPARG expression reversed the effect of miR-27b-3p overexpression. Mechanistically, miR-27b-3p regulated metastasis-related pathways through PPARG by promoting epithelial–mesenchymal transition. By suppressing PPARG, miR-27b-3p could also activate transcription factors Snail and NF-κB, thereby promoting metastasis.Conclusions: miR-27b-3p promotes TNBC progression and metastasis by inhibiting PPARG. MiR-27b-3p may be a potential prognostic marker of TNBC, and PPARG may be a potential molecular therapeutic target of TNBC.
Highlights
The role and underlying mechanisms of miR-27b-3p in triple-negative breast cancer (TNBC) remains unclear
Deregulated miRNAs are involved in extensive cellular processes of TNBC, exerting their function as oncogenes or tumor suppressors depending on their cellular targets [6]
In Kaplan-Meier survival analysis, the high miR-27b-3p expression group had a significantly shorter disease-free survival and overall survival than the low expression group (P < 0.001 and P = 0.005, respectively, Figures 1A,B). These results suggested the potential of miR-27b-3p as a prognostic marker of TNBC
Summary
The role and underlying mechanisms of miR-27b-3p in triple-negative breast cancer (TNBC) remains unclear. Deregulated miRNAs are involved in extensive cellular processes of TNBC, exerting their function as oncogenes or tumor suppressors depending on their cellular targets [6] One of these miRNAs is microRNA-27b-3p (miR-27b-3p), which has been found to primarily function as an oncogenic miRNA by targeting multiple tumor-suppressor genes in breast cancer [7]. Previous studies have reported that miR-27b-3p can suppress multiple target genes, such as NISCH (Nischarin protein) [8], ST-14 (suppression of tumorigenicity 14) [9], HIC1 (hypermethylated in cancer 1) [10], PSAP (prosaposin) [11], and PDHX (pyruvate dehydrogenase protein X) [12], to promote tumor progression and metastasis in breast cancer. In TNBC, the role of miR-27b-3p and its target pathways in tumor progression and metastasis is not fully understood and needs to be clarified
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