Han Jing, Xie Rongkai, Yang Ying, Chen Diangang, Liu Li, Wu Jiayang, Li Sufen
Department of Obstetrics and Gynecology, Xinqiao Hospital, Army Medical University, Chongqing, China.
Cancer Institute of PLA, Xinqiao Hospital, Army Medical University, Chongqing, China.
Transl Cancer Res. 2021 Sep;10(9):4076-4086. doi: 10.21037/tcr-21-175.
Ovarian cancer (OV) is a highly lethal disease, and the fifth leading cause of all cancer-related deaths in women. The study aimed to identify potential key genes associated with the proliferation and prognosis of OV.
Differentially expressed genes (DEGs) between ovarian cancer and normal tissues were screened by the robust rank aggregation (RRA) method. The expression of CENPA and MYBL2 were examined in SKOV3 and A2780 ovarian cancer cell lines and tumor tissues by qRT-PCR and western blot. Small RNA interference assays, plasmid overexpression assays and EdU assays were used to validate the proliferative effect of the MYBL2-CENPA axis in ovarian cancer cell lines. The ChIP assay was used to verify the direct regulation of MYBL2 on CENPA.
133 up-regulated genes and 158 down-regulated genes were identified, and the up-regulated genes mainly enrichment in cell cycle. The three up-regulated gene with DNA separation (CENPA, CENPF and CEP55) might be tightly correlated with proliferation and prognosis of OV. Knockdown CENPA expression inhibited the proliferation of A2780 and SKOV3 cells After the knockout of MYBL2, the expression of CENPA significantly decreased. MYBL2 directly binds to the promoter region of CENPA.
The MYBL2-CENPA pathway plays an important role in the proliferation of ovarian cancer cells, suggesting that this pathway may be a potential target for the treatment of ovarian cancer.
卵巢癌（OV）是一种致死率很高的疾病，是女性所有癌症相关死亡的第五大主要原因。本研究旨在鉴定与OV增殖和预后相关的潜在关键基因。
采用稳健秩聚合（RRA）方法筛选卵巢癌组织与正常组织之间的差异表达基因（DEG）。通过qRT-PCR和蛋白质印迹法检测CENPA和MYBL2在SKOV3和A2780卵巢癌细胞系及肿瘤组织中的表达。使用小RNA干扰试验、质粒过表达试验和EdU试验验证MYBL2-CENPA轴在卵巢癌细胞系中的增殖作用。采用染色质免疫沉淀试验验证MYBL2对CENPA的直接调控作用。
鉴定出133个上调基因和158个下调基因，上调基因主要富集于细胞周期。三个与DNA分离相关的上调基因（CENPA、CENPF和CEP55）可能与OV的增殖和预后密切相关。敲低CENPA表达可抑制A2780和SKOV3细胞的增殖。敲除MYBL2后，CENPA的表达显著降低。MYBL2直接结合CENPA的启动子区域。
MYBL2-CENPA通路在卵巢癌细胞增殖中起重要作用，提示该通路可能是卵巢癌治疗的潜在靶点。
