Department of Breast Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, Liaoning, PR China.
Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, PR China.
Exp Cell Res. 2022 Aug 1;417(1):113194. doi: 10.1016/j.yexcr.2022.113194. Epub 2022 May 4.
Breast cancer (BC) is the second cause of cancer-related mortality in women. Seizure related 6 homolog like 2 (SEZ6L2), a protein presented on cell surface, is involved in tumor development. It was found to be highly expressed in BC, however, its role in BC remains unclear. Herein, we aimed to explore the role of SEZ6L2 in BC. Firstly, the correlationship between SEZ6L2 expression and the clinic pathological characteristics of patients diagnosed with BC was analyzed. Subsequently, the role of SEZ6L2 was further explored using MTT, transwell invasion, flow cytometry, colony formation and wound healing assays. The result showed that the level of SEZ6L2 was remarkably correlated with the TNM stage, HER-2 status and lymph node metastasis of BC. Knockdown of SEZ6L2 significantly suppressed the proliferation of BC cells and induced cell cycle arrest at G1 phase. In addition, SEZ6L2 knockdown repressed their migration and invasion. On the contrary, SEZ6L2 overexpression performed the opposite effects. Furthermore, SEZ6L2 also accelerated the in vivo tumorigenesis of BC cells. Additionally, according to bioinformatics resources, we identified upstream transcription factor 1 (USF1) as a transcriptional factor which bound to the promoter of SEZ6L2 and positively regulated its transcription. In conclusion, this study demonstrated that SEZ6L2 was transcriptionally regulated by USF1 and was involved in the growth and metastasis of BC cells. Revealing the role of SEZ6L2 in BC provides additional knowledge for the pathogenesis of BC, which may benefit to BC therapy.
乳腺癌（BC）是女性癌症相关死亡的第二大原因。位于细胞表面的癫痫相关 6 同源物样 2（SEZ6L2）是一种蛋白质，参与肿瘤的发展。研究发现其在 BC 中高表达，但其在 BC 中的作用尚不清楚。在此，我们旨在探讨 SEZ6L2 在 BC 中的作用。首先，分析了 SEZ6L2 表达与诊断为 BC 的患者临床病理特征之间的相关性。随后，通过 MTT、Transwell 侵袭、流式细胞术、集落形成和划痕愈合实验进一步探讨 SEZ6L2 的作用。结果表明，SEZ6L2 水平与 BC 的 TNM 分期、HER-2 状态和淋巴结转移显著相关。SEZ6L2 敲低显著抑制 BC 细胞的增殖，并诱导细胞周期停滞在 G1 期。此外，SEZ6L2 敲低抑制其迁移和侵袭。相反，SEZ6L2 过表达则产生相反的效果。此外，SEZ6L2 还加速了 BC 细胞的体内致瘤性。此外，根据生物信息学资源，我们确定上游转录因子 1（USF1）作为与 SEZ6L2 启动子结合并正向调节其转录的转录因子。综上所述，本研究表明 SEZ6L2 受 USF1 转录调控，参与 BC 细胞的生长和转移。揭示 SEZ6L2 在 BC 中的作用为 BC 的发病机制提供了更多的知识，可能有益于 BC 的治疗。
