RYBP inhibits esophageal squamous cell carcinoma proliferation through downregulating CDC6 and CDC45 in G1-S phase transition process

• Published in: Life sciences (1973) 2020-06, Vol.250, p.117578-10, Article 117578
• Main Authors: Ke, Yue, Guo, Wei, Huang, Shan, Li, Yuxing, Guo, Yuyan, Liu, Xiaoxiao, Jin, Yingying, Ma, Hongbing
• Format: Article
• Language: English
• Subjects: Aged; Animals; Anticancer properties; Arrays; Cancer; CDC45; Cdc45 protein; CDC6; Cell cycle; Cell Cycle Proteins - metabolism; Cell Line, Tumor; Cell Proliferation; Deoxyribonucleic acid; DNA; DNA biosynthesis; DNA microarrays; Down-Regulation; Embryogenesis; Embryonic growth stage; Epigenetics; Esophageal cancer; Esophageal Neoplasms - metabolism; Esophageal Neoplasms - pathology; Esophageal squamous cell carcinoma; Esophageal Squamous Cell Carcinoma - metabolism; Esophageal Squamous Cell Carcinoma - pathology; Esophagus; Female; Flow cytometry; G1 Phase; Gene expression; Gene Expression Regulation, Neoplastic; Gene flow; Humans; Immunohistochemistry; In vivo methods and tests; Male; Mice; Mice, Nude; Middle Aged; Molecular modelling; Neoplasm Transplantation; Nuclear Proteins - metabolism; Oligonucleotide Array Sequence Analysis; Phase transitions; Polymerase chain reaction; Repressor Proteins - metabolism; RYBP; S Phase; Squamous cell carcinoma; Tissue Array Analysis; Transcriptome; YY1 protein
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2020.117578

RING1 and YY1-binding protein (RYBP) is an epigenetic regulator and plays crucial roles in embryonic development. The anti-tumor effect of RYBP has been reported in several cancers recently, but the role of RYBP in esophageal squamous cell carcinoma (ESCC) has not been fully elucidated. The present study aimed to investigate the biological function and the underlying molecular mechanisms of RYBP in ESCC. We detected the expression of RYBP in ESCC tissue microarrays (TMA) by immunohistochemistry. Cell proliferation was assessed by CCK8 and colony formation assays. Cell cycle was analyzed by flow cytometry. Gene expression was determined by transcriptome arrays, quantitative real-time PCR (qRT-PCR) and Western blot. Four-week-old male nude mice were used to evaluate the effect of RYBP in ESCC growth. We found that RYBP was downregulated in ESCC compared with adjacent normal tissues. A high level of RYBP expression predicted a better outcome of ESCC patients. Furthermore, overexpression of RYBP inhibited ESCC growth both in vitro and in vivo. Transcriptome arrays and functional studies showed that RYBP decreased the expression of genes related to cell cycles, especially CDC6 and CDC45, which were essential to initiate the DNA replication and G1-S transition. Taken together, our study suggests that RYBP suppresses ESCC proliferation by downregulating CDC6 and CDC45, thus inhibiting the G1-S transition.