Affiliation:
1. Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan China
Abstract
AbstractHigh grade serous ovarian carcinoma (HGSOC) is lethal with insidious onset, rapid progression, poor prognosis, and limited treatment options. Polycomb repressor complexes (PRC) 1 and 2 are intimately involved in progression of many types of cancer including HGSOC. Unlike the consistent constitution of PRC2, PRC1 consists of diverse components whose clinical significance in HGSOC are not entirely clear. Here, prognosis‐associated PRC1 components were identified through data‐mining. CBX2 promoted proliferation and reduced apoptosis of HGSOC cell lines OVCAR4, OVCAR3, and CAOV3. Complete loss of CBX2 by CRISPR‐cas9 editing (CBX2KO) destabilized genome stability with increased spontaneous chromosomal breaks and tendency to polyploidy accompanied by disrupted cell cycle especially stalled G2/M transition and caused severe cell death. Wnt/β‐catenin/LEF1/TCF7L1 was activated in surviving OVCAR4‐CBX2KO clones to bypass the crisis caused by loss of CBX2. The relieve of TCF7L1 core‐promoter region occupied by CBX2 might be one of the possible explanations to TCF7L1 increase in OVCAR4‐CBX2KO clones. Subcutaneous tumor model further validated that depletion of CBX2 repressed HGSOC cell line derived tumor growth. High immunohistochemistry score of CBX2 in primary ovarian cancer tissue associated with advanced clinical stage (p = 0.033), poor overall survival (HR = 3.056, 95% CI: 1.024−9.123), and progression free survival (HR = 4.455, 95% CI: 1.513−13.118) in HGSOC. Overall, our results suggested that CBX2 was a promising prognostic factor and therapeutic target in HGSOC.
Funder
National Natural Science Foundation of China
Subject
Cancer Research,Molecular Biology
Cited by
1 articles.
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