Triple-negative breast cancer (TNBC), characterized by high aggression and invasiveness, has a worse prognosis than other subtypes of breast cancer. Establishing a novel animal model is helpful to understand the mechanisms involved in the progress of TNBC metastasis. In a self-established mouse model consisting normal human breast tissues and normal human bone tissues, TNBC cell line SUM-1315 could spontaneously form species-specific bone metastasis. The expression level of miR-1976 in SUM-1315-bo (derived from metastatic bone tumor) was found lower than that in SUM-1315-br (derived from orthotopic breast tumor). MiR-1976 was found to be downregulated in TNBC tissues, and lower expression of miR-1976 was correlated with worse overall survival in a patient cohort obtained from TCGA database. MiR-1976 knockdown promoted epithelial–mesenchymal transition (EMT) and cancer stem cell (CSC) properties in vitro and in vivo. Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma (PIK3CG) was verified as a target gene by sequencing, biotinylated miRNA pull-down, and luciferase reporter assay. Moreover, overexpression and suppression analysis implicated PIK3CG as a mediator of the biological effects of miR-1976. Our study demonstrated that miR-1976 knockdown could promote EMT and CSCs by PIK3CG. These findings may reveal mechanisms of TNBC metastasis, and represent a potential treatment target for patients with TNBC.

具有高侵略性和侵袭性的三阴性乳腺癌（TNBC）的预后比其他亚型的乳腺癌差。建立一种新颖的动物模型有助于了解TNBC转移进展的机制。在由正常人的乳腺组织和正常人的骨组织组成的自建小鼠模型中，TNBC细胞系SUM-1315可以自发形成物种特异性骨转移。发现miR-1976在SUM-1315-bo（源自转移性骨肿瘤）中的表达水平低于SUM-1315-br（源自原位乳腺肿瘤）。发现在TNBC组织中MiR-1976被下调，而从TCGA数据库获得的患者队列中miR-1976的较低表达与较差的总体生存率相关。在体外和体内，MiR-1976基因敲低促进了上皮-间质转化（EMT）和癌症干细胞（CSC）特性。通过测序，生物素化的miRNA下拉和荧光素酶报告基因分析，验证了磷脂酰肌醇-4,5-双磷酸3-激酶催化亚基γ（PIK3CG）作为靶基因。此外，过度表达和抑制分析暗示PIK3CG是miR-1976生物学效应的介体。我们的研究表明，miR-1976基因敲低可以通过PIK3CG促进EMT和CSC。这些发现可能揭示了TNBC转移的机制，并代表了TNBC患者的潜在治疗目标。生物素化的miRNA下拉和荧光素酶报告基因检测。此外，过度表达和抑制分析暗示PIK3CG是miR-1976生物学效应的介体。我们的研究表明，miR-1976基因敲低可以通过PIK3CG促进EMT和CSC。这些发现可能揭示了TNBC转移的机制，并代表了TNBC患者的潜在治疗目标。生物素化的miRNA下拉和荧光素酶报告基因检测。此外，过度表达和抑制分析表明PIK3CG是miR-1976生物学效应的介体。我们的研究表明，miR-1976基因敲低可以通过PIK3CG促进EMT和CSC。这些发现可能揭示了TNBC转移的机制，并代表了TNBC患者的潜在治疗目标。