%0 Journal Article
%T CCNG1 (Cyclin G1) regulation by mutant©\P53 via induction of Notch3 expression promotes high©\grade serous ovarian cancer (HGSOC) tumorigenesis and progression
%A Beihua Kong
%A Chenjuan Jin
%A Chunying Miao
%A Qing Zhang
%A Ruifeng Dong
%A Samina Dongol
%A Xingsheng Yang
%A Ying Xu
%A Yingwei Li
%A Yinuo Li
%J Archive of "Cancer Medicine".
%D 2019
%R 10.1002/cam4.1812
%X TP53 mutation is considerably common in advanced high©\grade serous ovarian cancer (HGSOC) and significantly associated with a poor prognosis. In this study, we investigated the role of Cyclin G1 (CCNG1), a target gene of wild©\type TP53 (P53wt), in HGSOC and the possible regulatory mechanism between TP53 mutant (P53mt) and CCNG1 in the progression of HGSOC. High expression level of CCNG1 was found in 61.3% of HGSOC tissues and only 18.2% in fimbriae of fallopian tubes. Additionally, overexpression of CCNG1 was significantly associated with a shorter overall survival (P < 0.0001) and progression©\free survival (P < 0.0004) in HGSOC patients. In vitro, CCNG1 promoted both tumor cell motility by inducing epithelial©\mesenchymal transition (EMT) and resistance to cisplatin (CDDP). In vivo, knockdown expression of CCNG1 inhibited cancer metastasis. Furthermore, P53mt increased the expression of CCNG1 by regulating Notch3 expression, and a positive correlation between CCNG1 and Notch3 protein expression was observed by Immunohistochemistry (IHC) (r = 0.39, P: 0.01528). In conclusion, the activation of P53mt©\Notch3©\CCNG1 pathway was responsible for tumor progression to advanced disease with correlation with worse prognosis in patients with HGSOC. These data suggest a possible molecular mechanism of disease and highlights CCNG1¡¯s potential role as a therapeutic target in HGSOC
%K Cyclin G1
%K high©\grade serous ovarian cancer
%K metastasis
%K Notch3
%K P53mt
%K prognosis
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6346265/