miR‑574‑5p attenuates proliferation, migration and EMT in triple‑negative breast cancer cells by targeting BCL11A and SOX2 to inhibit the SKIL/TAZ/CTGF axis.

Abstract	Triple‑negative breast cancer (TNBC) is a subtype of breast cancer with a high degree of malignancy. TNBC is prone to distant metastasis and has a poor prognosis. A number of TNBC‑related microRNAs (miRNAs) have been studied and identified. However, the detailed roles of miR‑574‑5p in TNBC remain poorly understood. miR‑574‑5p, SRY (sex determining region Y)‑box 2 (SOX2), B‑cell lymphoma/leukaemia 11A (BCL11A), SKI like proto‑oncogene (SKIL) and epithelial‑mesenchymal transition (EMT)‑related miRNAs and proteins were measured by reverse transcription‑quantitative PCR and western blotting analysis, respectively. A luciferase reporter assay was employed to validate the direct targeting of SOX2 and BCL11A by miR‑574‑5p. MTT, colony formation and Transwell assays were performed to analyse the biological functions of miR‑574‑5p in TNBC cells. A nude mouse xenograft model was used to verify the effects of miR‑574‑5p on the tumorigenesis of TNBC in vivo. The results demonstrated that miR‑574‑5p levels were decreased in breast cancer tissues and cells. miR‑574‑5p repressed proliferation, migration and EMT in TNBC cells. Further experiments confirmed that miR‑574‑5p reduced tumour size and metastasis in vivo. miR‑574‑5p targeted BCL11A and SOX2 to inhibit the SKIL/transcriptional co‑activator with PDZ‑binding motif/connective tissue growth factor axis, and the inhibitory effect of miR‑574‑5p in TNBC cells was at least partly dependent on SOX2 and BCL11A. In addition, the regulation of downstream oncogenes by SOX2 was dependent on BCL11A. To the best of our knowledge, this is the first study to report the association between the miR‑574‑5p/BCL11A/SOX2 axis and the tumorigenesis of TNBC, which provides a new mechanism for understanding the progression of TNBC.
Authors	Ke-Jing Zhang, Yu Hu, Na Luo, Xin Li, Fei-Yu Chen, Jia-Qi Yuan, Lei Guo
Journal	International journal of oncology (Int J Oncol) Vol. 56 Issue 5 Pg. 1240-1251 (05 2020) ISSN: 1791-2423 [Electronic] Greece
PMID	32319565 (Publication Type: Journal Article)
Chemical References	BCL11A protein, human CCN2 protein, human Intracellular Signaling Peptides and Proteins MAS1 protein, human MIRN574 microRNA, human MicroRNAs Proto-Oncogene Mas Proto-Oncogene Proteins Repressor Proteins SKIL protein, human SOX2 protein, human SOXB1 Transcription Factors Trans-Activators Transcriptional Coactivator with PDZ-Binding Motif Proteins WWTR1 protein, human Connective Tissue Growth Factor
Topics	Adult Aged Animals Cell Line, Tumor Cell Movement Cell Proliferation Connective Tissue Growth Factor (metabolism) Down-Regulation Epithelial-Mesenchymal Transition Female Gene Expression Regulation, Neoplastic Humans Intracellular Signaling Peptides and Proteins (metabolism) Mice MicroRNAs (genetics) Middle Aged Neoplasm Transplantation Proto-Oncogene Mas Proto-Oncogene Proteins (metabolism) Repressor Proteins (genetics, metabolism) SOXB1 Transcription Factors (genetics, metabolism) Trans-Activators (metabolism) Transcriptional Coactivator with PDZ-Binding Motif Proteins Triple Negative Breast Neoplasms (genetics, metabolism, pathology) Tumor Burden

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