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GATA1-regulated JAG1 promotes ovarian cancer progression by activating Notch signal pathway
Protoplasma ( IF 2.5 ) Pub Date : 2020-01-03 , DOI: 10.1007/s00709-019-01477-w
Zhenzhen Liu 1 , Yongchun Zhu 2 , Fangfang Li 2 , Yuge Xie 1
Affiliation  

Ovarian cancer is the major cause of mortality due to late stage diagnoses and lower survival rates, and the mechanism of cancer progression is not completely understood. Thus, exploring the regulatory factors of ovarian cancer proliferation and metastasis is urgent. JAG1 expression in KOV3 and OVCA433 cells was detected by qPCR and western blot. MTT and Transwell assays were used to determine cell proliferation and metastasis. The tumor spheres formation assay, DOX, and Cisplatin administrations were performed to assess JAG1-induced stemness and chemoresistance. ChIP assay was used to verify the direct binding of GATA1 on JAG1 promoter. Ovarian cancer cells have higher JAG1 expression, which turns on Notch signaling and promotes cell proliferation, migration, invasion, stemness, and the resistance of chemotherapy. While knockdown JAG1 dramatically suppressed the ovarian cancer progression, GATA1 is the transcriptional factor of JAG1 in ovarian cells, knockdown JAG1 can inhibit GATA1-induced Notch activation and cell proliferation. This study demonstrates that JAG1, acting as an oncogenic gene, plays an important role in ovarian cancer progression and chemoresistance. Targeting GATA1/JAG1/Notch pathway may provide a novel strategy for ovarian cancer treatment.

中文翻译:

GATA1调控的JAG1通过激活Notch信号通路促进卵巢癌进展

由于晚期诊断和较低的存活率,卵巢癌是死亡的主要原因,并且癌症进展的机制尚不完全清楚。因此,探索卵巢癌增殖转移的调控因素迫在眉睫。通过 qPCR 和蛋白质印迹检测 KOV3 和 OVCA433 细胞中 JAG1 的表达。MTT和Transwell测定用于确定细胞增殖和转移。进行肿瘤球形成测定、DOX 和顺铂给药以评估 JAG1 诱导的干细胞性和化学抗性。ChIP 测定用于验证 GATA1 与 JAG1 启动子的直接结合。卵巢癌细胞具有较高的 JAG1 表达,它打开 Notch 信号并促进细胞增殖、迁移、侵袭、干细胞和化疗耐药。虽然敲低 JAG1 显着抑制卵巢癌进展,但 GATA1 是卵巢细胞中 JAG1 的转录因子,敲低 JAG1 可以抑制 GATA1 诱导的 Notch 激活和细胞增殖。该研究表明,JAG1 作为致癌基因,在卵巢癌进展和化学耐药性中起重要作用。靶向 GATA1/JAG1/Notch 通路可能为卵巢癌治疗提供一种新策略。
更新日期:2020-01-03
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