Abstract

BackgroundTriple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer owing to a lack of effective targeted therapy and acquired chemoresistance. Here, we explored the function and mechanism of shank-interacting protein-like 1 (SIPL1) in TNBC progression.MethodsSIPL1 expression was examined in human TNBC tissues and cell lines by quantitative reverse transcription PCR, western blot, and immunohistochemistry. SIPL1 overexpression and silenced cell lines were established in BT-549 and MDA-MB-231 cells. The biological functions of SIPL1 in TNBC were studied in vitro using the CCK-8 assay, CellTiter-Glo Luminescent Cell Viability assay, caspase-3/8/9 assay, wound healing assay, and transwell assay and in vivo using a nude mouse model. The potential mechanisms underlying the effects of SIPL1 on TNBC progression were explored using bioinformatics analysis, luciferase reporter assays, and chromatin immunoprecipitation followed by qPCR.Results SIPL1 expression was higher in human TNBC tissues and cell lines than in adjacent normal tissues and a breast epithelial cell line (MCF10A). High expression of SIPL1 was positively correlated with poor overall and disease-free survival in patients with TNBC. SIPL1 overexpression elevated and SIPL1 silencing repressed the malignant phenotypes of TNBC cells in vitro. SIPL1 overexpression promoted xenograft tumor growth in vivo. Myc-associated zinc-finger protein (MAZ) transcriptionally activated SIPL1. Finally, we found that SIPL1 promoted TNBC malignant phenotypes via activation of the AKT/NF-κB signaling pathways.ConclusionsThese results indicate that the MAZ/SIPL1/AKT/NF-κB axis plays a crucial role in promoting the malignant phenotypes of TNBC cells.

Highlights

  • Breast cancer (BC) is the most commonly diagnosed malignancy in women, accounting for 10% of new malignancies diagnosed worldwide [1]

  • Shank-interacting protein-like 1 (SIPL1) overexpression elevated and SIPL1 silencing repressed the malignant phenotypes of Triple-negative breast cancer (TNBC) cells in vitro

  • These results indicate that the Myc-associated zinc-finger protein (MAZ)/SIPL1/AKT/NF-kB axis plays a crucial role in promoting the malignant phenotypes of TNBC cells

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Summary

Introduction

Breast cancer (BC) is the most commonly diagnosed malignancy in women, accounting for 10% of new malignancies diagnosed worldwide [1]. Quite a few studies have shown that SIPL1 is amplified and overexpressed in many types of human malignancies, such as breast cancer, gastric cancer, and melanoma [6,7,8], some studies have demonstrated the tumorsuppressive role of SIPL1 in esophageal cancer progression [9]. Zhou et al demonstrated that SIPL1 expression was elevated in human melanoma tissues and SIPL1 overexpression promoted melanoma development and progression via the p38 and c-Jun N-terminal kinases (JNK)/c-Jun signaling pathways [7]. In view of the wide-ranging roles of SIPL1 proposed in breast cancer, a comprehensive summary of the mechanisms by which SIPL1 regulates TNBC tumorigenesis has not been directly reported. We explored the function and mechanism of shank-interacting protein-like 1 (SIPL1) in TNBC progression

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