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

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 (TP53^wt/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.

SUBMITTER: Morinaka T

PROVIDER: S-EPMC10546375 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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

Morinaka Takashi T Sakai Nozomu N Takayashiki Tsukasa T Kuboki Satoshi S Takano Shigetsugu S Ohira Gaku G Matsubara Hisahiro H Ohtsuka Masayuki M

International journal of oncology 20230901 5

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 <i>TP53</i> gene status such as HCT ...[more]

PMID: 37654197

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Project description:BackgroundColorectal cancer (CRC) is the third most common of cancer-related deaths. Nucleolar protein 14 (NOP14) is known to play different roles in diverse types of cancers. However, little is known about its roles in CRC. Here, we assessed the prognostic value and functions of NOP14 in CRC using the data from The Cancer Genome Atlas (TCGA) and validated them based on the data from Gene Expression Omnibus (GEO).MethodsNOP14 mRNA and protein data in CRC was obtained from the TCGA, GEO, human protein atlas (HPA), and UALCAN databases. Survival and Cox regression analysis was performed to assess the prognostic value of NOP14 in CRC patients. Next, to evaluate the potential functions of NOP14, a protein-protein interaction (PPI) network was constructed and gene set enrichment analysis (GSEA) of differential expression genes (DEGs) associated with dysregulated NOP14 was performed. Finally, to investigate the immune response associated with NOP14 expression in CRC, we analyzed the correlations between immune cells infiltration and NOP14 expression level. Additionally, the correlations between immune molecule expression levels with NOP14 expression level were analyzed.ResultsHigh NOP14 mRNA expression was observed in CRC tissues based on the data from TCGA and GEO datasets. Similarly, high NOP14 protein levels were found in CRC tissues according to the immunohistochemical images from HPA. Interestingly, high NOP14 expression level was associated with an improved prognosis in CRC patients. Univariate and multivariate Cox regression analysis indicated that high NOP14 expression level was an independent protective factor for CRC patients. With the support of PPI network analysis, we found several risk genes interacted with NOP14. GSEA revealed that high NOP14 expression inhibited several signal pathways involved in tumor formation and development. Additionally, high NOP14 expression was positively associated with most kinds of immune cell infiltrations and the expression levels of some molecules related to immune activation.ConclusionAltogether, these results indicated that high NOP14 expression leads to improved prognosis in CRC patients by inhibiting the signaling pathways involved in tumor growth and promoting the immune responses.

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

Publications

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

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