Elevated expression of Copine 1 (CPNE1) has been observed in multiple cancers; however, the underlying mechanisms by which it affects cancer cells are unclear. We aimed to study the effect of CPNE1 on the tumorigenesis and radioresistance of triple-negative breast cancer (TNBC). Quantitative real-time polymerase chain reaction was used to detect the expression of CPNE1 in TNBC tissues and cell lines. Western blot, immunohistochemistry, and immunofluorescence were used to investigate the levels of CPNE1, p-AKT, AKT, cleaved caspase-3, cleaved PARP1, and γ-H2AX. Cell viability and apoptosis were measured by CCK-8 and flow cytometry, respectively. CPNE1 was overexpressed in TNBC tissues and cell lines and was associated with tumor size, distant metastases, and survival rates of patients with TNBC. Moreover, function study shows that CPNE1 promoted cell viability and inhibited cell apoptosis in vitro and inhibited the radiosensitivity of TNBC. Importantly, inactivation of AKT signaling inhibited the tumorigenesis and radioresistance mediated by CPNE1 in TNBC cells. In vivo xenograft study also shows that CPNE1 knockdown inhibited tumor growth and promoted cell apoptosis. Overall, our findings suggest that CPNE1 promotes tumorigenesis and radioresistance in TNBC by regulating AKT activation and targeted CPNE1 expression may be a strategy to sensitize TNBC cells toward radiation therapy.

中文翻译：

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CPNE1预测三阴性乳腺癌的预后不良，并通过AKT单一途径促进肿瘤发生和放射抵抗。

在多种癌症中均观察到了Copine 1（CPNE1）的高表达。然而，其影响癌细胞的潜在机制尚不清楚。我们旨在研究CPNE1对三阴性乳腺癌（TNBC）的肿瘤发生和放射抵抗的影响。实时定量聚合酶链反应用于检测CPNE1在TNBC组织和细胞系中的表达。免疫印迹，免疫组化和免疫荧光被用来研究CPNE1，p-AKT，AKT，裂解的caspase-3，裂解的PARP1和γ-H2AX的水平。细胞活力和凋亡分别通过CCK-8和流式细胞仪测量。CPNE1在TNBC组织和细胞系中过表达，并与TNBC患者的肿瘤大小，远处转移和存活率相关。此外，功能研究表明，CPNE1在体外可促进细胞活力并抑制细胞凋亡，并抑制TNBC的放射敏感性。重要的是，AKT信号的失活抑制了TNBC细胞中CPNE1介导的肿瘤发生和放射抗性。体内异种移植研究还显示，CPNE1基因敲低可抑制肿瘤生长并促进细胞凋亡。总体而言，我们的发现表明CPNE1通过调节AKT激活促进TNBC的肿瘤发生和放射抵抗，而靶向CPNE1的表达可能是使TNBC细胞对放射治疗敏感的策略。体内异种移植研究还显示，CPNE1基因敲低可抑制肿瘤生长并促进细胞凋亡。总体而言，我们的发现表明CPNE1通过调节AKT激活促进TNBC的肿瘤发生和放射抵抗，而靶向CPNE1的表达可能是使TNBC细胞对放射治疗敏感的策略。体内异种移植研究还显示，CPNE1基因敲低可抑制肿瘤生长并促进细胞凋亡。总体而言，我们的发现表明CPNE1通过调节AKT激活促进TNBC的肿瘤发生和放射抵抗，而靶向CPNE1的表达可能是使TNBC细胞对放射治疗敏感的策略。