GATA1-regulated JAG1 promotes ovarian cancer progression by activating Notch signal pathway.

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.

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