RYBP通过调控细胞周期、细胞凋亡和奥沙利铂敏感性,为结直肠癌患者的预后提供了改善。
RYBP contributes to improved prognosis in colorectal cancer via regulation of cell cycle, apoptosis and oxaliplatin sensitivity.
发表日期:2023 Nov
作者:
Takashi Morinaka, Nozomu Sakai, Tsukasa Takayashiki, Satoshi Kuboki, Shigetsugu Takano, Gaku Ohira, Hisahiro Matsubara, Masayuki Ohtsuka
来源:
Epigenetics & Chromatin
摘要:
Ring1和YY-1结合蛋白(RYBP)是聚合酶抑制复合物1的成员,并通过表观遗传修饰起到转录抑制作用。RYBP在固体肿瘤中具有抑制肿瘤的作用,但其在结直肠癌(CRC)中的功能尚不清楚。本研究通过免疫组织化学方法在140例原发性CRC和11例肝转移病例中评估了RYBP的表达情况。使用具有不同TP53基因状态的CRC细胞系,如HCT116(TP53wt/wt)、HCT116(TP53-/-)、SW48和DLD-1细胞,评估了细胞增殖、细胞周期进展、细胞凋亡以及RYBP对奥沙利铂敏感性的影响。临床数据显示,RYBP低表达与远处转移和复发风险显著相关,RYBP高表达患者的癌症特异性和无病生存显著更好。体外实验表明,RYBP通过诱导细胞周期停滞和细胞凋亡抑制了TP53野生型细胞的增殖。此外,内源性RYBP过表达增强了奥沙利铂的敏感性。因此,RYBP可能通过调节细胞周期、细胞凋亡和奥沙利铂敏感性的p53介导途径,对CRC的预后改善起到贡献。
Ring1 and YY‑1 binding protein (RYBP) is a member of the polycomb repressive complex 1 and serves as a transcriptional suppressor via epigenetic modification. RYBP has a tumour‑suppressive role in solid tumours, but its function in colorectal cancer (CRC) remains unknown. The present study evaluated the expression of RYBP using immunohistochemistry in 140 cases of primary CRC and 11 patient‑matched cases of liver metastases. Using CRC cell lines with different TP53 gene status such as HCT116 (TP53wt/wt), HCT116 (TP53‑/‑), SW48 and DLD‑1 cells, proliferation, cell cycle progression and apoptosis, as well as the effect of RYBP on oxaliplatin sensitivity, were assessed. Clinical data showed that low RYBP expression was significantly associated with risk of distant metastasis and recurrence, and patients with high RYBP expression demonstrated significantly better cancer‑specific and disease‑free survival. In vitro experiments revealed that RYBP suppressed cell proliferation by inducing cell cycle arrest and apoptosis in TP53 wild‑type cells. In addition, endogenous RYBP overexpression enhanced sensitivity to oxaliplatin. Therefore, RYBP may contribute to improved prognosis in CRC by regulating the cell cycle, apoptosis and oxaliplatin sensitivity via the p53‑mediated pathway.