Mir-130A-3P Blocks Wnt Signaling Cascade in the Triple-Negative Breast Cancer by Targeting the Key Players at Multiple Points Publisher



Poodineh J¹ ; Siratisabet M¹ ; Rajabibazl M^{1, 2} ; Mohammadiyeganeh S^{2, 3}
Source: Heliyon Published:2020

Abstract

Cell biology; Bioinformatics; Biotechnology; Biochemistry; Molecular biology; Cancer research; Triple-negative breast cancer; miR-130a-3p; Wnt/β-catenin; ZEB1; FZD6; LRP6. © 2020 The Author(s); Objectives: Aberrant Wnt signaling cascade is a hallmark of the triple-negative breast cancer (TNBC) that is linked with the increased proliferation, invasion, and poor overall survival. many genes are post-transcriptionally regulated by microRNAs (miRNAs) therefore; it is indisputable that the dysregulation of the miRNAs is an explanation for the aberrant signaling cascades. Thus, the present study was conducted to find the putative miRNA targeting the key players of Wnt/β -catenin cascade in the TNBC. Methods: The miR-130a-3p was found as a potential regulator of the Wnt signaling cascade by applying several bioinformatic algorithms. Quantitative real-time PCR (qRT-PCR) was used to analyze the expression levels of miR-130a-3p and Wnt cascade genes in the TNBC cells. Afterward, TNBC cells were transiently transfected with the miR-130a-3p to investigate its effects on the expression of Wnt cascade genes. Subsequently, MTT, soft agar colony formation, scratch, transwell cell migration, and transwell cell invasion assays were used to determine the behavior of the TNBC cells in response to miR-130a-3p restoration. Results: Results of the qRT-PCR showed downregulation of miR-130a-3p and upregulation of the Wnt cascade genes in the TNBC cells compared to the normal cells. Transient overexpression of miR-130a-3p decreased the expression levels of Wnt cascade genes significantly in the TNBC cells. Moreover, following the miR-130a-3p overexpression, the proliferation, anchorage-independent growth, and migration of the TNBC cells were reduced. Conclusion: Overall, our findings provided an evidence for the significant role of miR-130a-3p in the regulation of Wnt/β-catenin cascade, and also introduced the miR-130a-3p as a new therapeutic target for the patients with TNBC. © 2020 The Author(s)