DKC1 enhances angiogenesis by promoting HIF-1α transcription and facilitates metastasis in colorectal cancer
DKC1 enhances angiogenesis by promoting HIF-1α transcription and facilitates metastasis in colorectal cancer
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DKC1 通过促进 HIF-1 α 转录增强血管生成并促进结直肠癌转移
DOI：
10.1038/s41416-019-0695-z
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发表时间：
2020-03-01
影响因子：
8.8
通讯作者：
Song, Jun
中科院分区：
文献类型：
--
作者：
Hou, Pingfu;Shi, Peicong;Song, Jun
背景先天性角化不良1（DKC 1）在多种肿瘤中表达异常。方法应用组织芯片技术检测411例结直肠癌及癌旁组织中DKC 1的表达。进一步分析DKC 1表达与临床病理及生存期的关系。通过一系列的体内外实验研究DKC 1在结直肠癌中的作用及其分子机制。DKC 1表达增高与大肠癌TNM分期高、淋巴结转移多、预后差有关。多变量考克斯分析表明DKC 1可以作为CRC患者的独立预后因素。DKC 1还通过增加HIF-1α和VEGF表达水平促进CRC血管生成和转移。结论DKC 1可能通过直接激活HIF-1α的转录而调控大肠癌的血管生成和转移。DKC 1可作为预测结直肠癌患者预后的一个准确指标，并可作为潜在的治疗靶点。
BackgroundDyskeratosis congenita 1 (DKC1) is dysregulated in several cancers. However, the expression and function of DKC1 in colorectal cancer (CRC) is rarely reported.MethodsTissue microarrays (TAMs) including 411 cases of CRC tissues and corresponding paracancerous tissues were used to examine the DKC1 expression. The correlations between the DKC1 expression and clinicopathological or survival characters were further analysed. The functions and molecular mechanism of DKC1 in CRC were investigated through a series of in vitro and in vivo experiments.ResultsThe result showed that DKC1 expression was increased in CRC tissues. Increased DKC1 expression was associated with high grade of TNM stage, additional lymph node metastasis, and poor prognosis of patients with CRC. Multivariate COX analysis indicated that DKC1 can act as an independent prognostic factor for patients with CRC. DKC1 also facilitated the CRC angiogenesis and metastasis by increasing HIF-1α and VEGF expression levels. Chromatin immunoprecipitation assay demonstrated that DKC1 facilitated HIF-1α expression by regulating HIF-1α promoter activity.ConclusionDKC1 appears to regulate CRC angiogenesis and metastasis through directly activating HIF-1α transcription. DKC1 can serve as an accurate indicator in predicting the prognosis of patients with CRC and act as a potential therapeutic target for CRC.