RYBP contributes to improved prognosis in colorectal cancer via regulation of cell cycle, apoptosis and oxaliplatin sensitivity

RYBP 通过调节细胞周期、细胞凋亡和奥沙利铂敏感性有助于改善结直肠癌的预后

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作者:Takashi Morinaka, Nozomu Sakai, Tsukasa Takayashiki, Satoshi Kuboki, Shigetsugu Takano, Gaku Ohira, Hisahiro Matsubara, Masayuki Ohtsuka

Abstract

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.

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