AUTHOR=He Juanjuan , Wang Jing , Li Teng , Chen Kunlun , Li Songchao , Zhang Shaojin 

TITLE=SIPL1, Regulated by MAZ, Promotes Tumor Progression and Predicts Poor Survival in Human Triple-Negative Breast Cancer

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.766790

DOI=10.3389/fonc.2021.766790

ISSN=2234-943X

ABSTRACT=<sec><title>Background</title><p>Triple-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.</p></sec><sec><title>Methods</title><p>SIPL1 expression was examined in human TNBC tissues and cell lines by quantitative reverse transcription PCR, western blot, and immunohistochemistry. <italic>SIPL1</italic> overexpression and silenced cell lines were established in BT-549 and MDA-MB-231 cells. The biological functions of SIPL1 in TNBC were studied <italic>in vitro</italic> using the CCK-8 assay, CellTiter-Glo Luminescent Cell Viability assay, caspase-3/8/9 assay, wound healing assay, and transwell assay and <italic>in vivo</italic> 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.</p></sec><sec><title>Results</title><p><italic>SIPL1</italic> 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 <italic>SIPL1</italic> was positively correlated with poor overall and disease-free survival in patients with TNBC. <italic>SIPL1</italic> overexpression elevated and <italic>SIPL1</italic> silencing repressed the malignant phenotypes of TNBC cells <italic>in vitro</italic>. <italic>SIPL1</italic> overexpression promoted xenograft tumor growth <italic>in vivo</italic>. Myc-associated zinc-finger protein (MAZ) transcriptionally activated <italic>SIPL1</italic>. Finally, we found that SIPL1 promoted TNBC malignant phenotypes <italic>via</italic> activation of the AKT/NF-κB signaling pathways.</p></sec><sec><title>Conclusions</title><p>These results indicate that the MAZ/SIPL1/AKT/NF-κB axis plays a crucial role in promoting the malignant phenotypes of TNBC cells.</p></sec>