RNF8 induces β-catenin-mediated c-Myc expression and promotes colon cancer proliferation

RNF8 induces β-catenin-mediated c-Myc expression and promotes colon cancer proliferation
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RNF8诱导β-连环蛋白介导的c-Myc表达并促进结肠癌增殖

DOI:
10.7150/ijbs.44119
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发表时间:
2020-01-01
影响因子:
9.2
通讯作者:
Xing, Chengzhong
Xing, Chengzhong
中科院分区:
生物学2区
文献类型:
--
作者:
Ren, Ling;Zhou, Tingting;Xing, Chengzhong

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DNA损伤信号传感器环手指蛋白8(RNF8)通过通过泛素信号传导促进DNA双链断裂(DSB)来维持基因组稳定性。通过分析TCGA数据库和结肠癌组织微阵列,我们发现RNF8的表达水平与结肠癌中C-MYC的表达水平呈正相关,这些表达与结肠癌患者的存活不良密切相关。此外,过表达和击倒RNF8分别增加和降低了结肠癌细胞中C-MYC的表达。此外,RNF8与β-catenin相互作用,并通过将K63多泛素化在其上促进其核转运。这些观察结果表明,RNF8通过诱导β-catenin介导的C-MYC表达来促进结肠癌的进展。
DNA damage signals transducer RING finger protein 8 (RNF8) is involved in maintaining genomic stability by facilitating the repair of DNA double-strand breaks (DSB) via ubiquitin signaling. By analyzing the TCGA database and colon cancer tissue microarrays, we found that the expression level of RNF8 was positively correlated with that of c-Myc in colon cancer, which were closely associated with poor survival of colon cancer patients. Furthermore, overexpressing and knocking down RNF8 increased and decreased the expression of c-Myc in colon cancer cells, respectively. In addition, RNF8 interacted with beta-catenin and facilitated its nuclear translocation by conjugating K63 polyubiquitination on it. These observations suggested a de novo role of RNF8 in promoting the progression of colon cancer by inducing beta-catenin-mediated c-Myc expression.