PCLAF promotes neuroblastoma G1/S cell cycle progression via the E2F1/PTTG1 axis |
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| Authors: | Xiaowei Liu Yuanxia Cai Cheng Cheng Yaoyao Gu Xiaoxiao Hu Kai Chen Yeming Wu Zhixiang Wu |
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| Affiliation: | 1.Department of Pediatric Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200092 China ;2.Division of Pediatric Oncology, Shanghai Institute of Pediatric Research, Shanghai, 200092 China ;3.Department of Pediatric Surgery, Children’s Hospital of Soochow University, Suzhou, 215003 China |
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| Abstract: | PCLAF (PCNA clamp-associated factor), also known as PAF15/ KIAA0101, is overexpressed in most human cancers and is a predominant regulator of tumor progression. However, its biological function in neuroblastoma remains unclear. PCLAF is extremely overexpressed in neuroblastoma and is associated with poor prognosis. Through the analysis of various data sets, we found that the high expression of PCLAF is positively correlated with increased stage and high risk of neuroblastoma. Most importantly, knocking down PCLAF could restrict the proliferation of neuroblastoma cells in vitro and in vitro. By analyzing RNA-seq data, we found that the enrichment of cell cycle-related pathway genes was most significant among the differentially expressed downregulated genes after reducing the expression of PCLAF. In addition, PCLAF accelerated the G1/S transition of the neuroblastoma cell cycle by activating the E2F1/PTTG1 signaling pathway. In this study, we reveal the mechanism by which PCLAF facilitates cell cycle progression and recommend that the PCLAF/E2F1/PTTG1 axis is a therapeutic target in neuroblastoma.Subject terms: Cancer epigenetics, Cell growth |
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