Cleavage and polyadenylation specific factor 4 promotes colon cancer progression by transcriptionally activating hTERT
Cleavage and polyadenylation specific factor 4 promotes colon cancer progression by transcriptionally activating hTERT
复制标题
裂解和聚腺苷酸化特异性因子 4 通过转录激活 hTERT 促进结肠癌进展
DOI：
10.1016/j.bbamcr.2019.07.001
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发表时间：
2019-10-01
影响因子：
5.1
通讯作者：
Wu, Xiaojun
中科院分区：
文献类型：
--
作者：
Yang, Qian;Fan, Wenhua;Wu, Xiaojun
CPSF 4被认为是肺癌发生的关键致瘤因子。然而，其在结肠癌进展中的确切功能和潜在分子机制仍然完全未知。在这里，我们证明CPSF 4在人结肠癌细胞和组织中高度表达。在体外，它的敲低抑制结直肠癌的进展，包括细胞增殖、迁移、侵袭和干性维持。相反，CPSF 4的异位过表达在体外和体内具有相反的作用。进一步的机制研究表明，CPSF 4通过与NF-κ B 1协同转录调控hTERT的表达，并与hTERT启动子-321 ~-234片段共锚定，促进大肠癌的发生发展。此外，临床样本分析表明，CPSF 4表达与hTERT正相关，CPSF 4和hTERT同时高表达预示患者预后不良。总体而言，我们的研究结果确立了CPSF 4作为结直肠癌进展中的促肿瘤发生因子，并表明靶向CPSF 4-hTERT轴可能代表结肠癌治疗中有希望的治疗策略。
CPSF4 was identified as a crucial tumorigenic factor in lung cancer development. However, its precise function and the underlying molecular mechanisms in colon cancer progression remain completely unknown. Here, we demonstrate CPSF4 was highly expressed in human colon cancer cells and tissues. Its knockdown inhibited colorectal cancer progression in vitro, including cell proliferation, migration, invasion and stemness maintenance. In contrast, the ectopic overexpression of CPSF4 had the opposite effects in vitro and in vivo. Further mechanistic studies demonstrated that CPSF4 facilitated colorectal tumorigenesis and development partially through transcriptionally regulating hTERT expression by cooperating with NF-kB1 and co-anchoring at hTERT promoter -321 to -234 fragment. In addition, clinical samples analysis indicated that CPSF4 expression was positively correlated with hTERT, and the simultaneously high expression of CPSF4 and hTERT predicted poor patient outcome. Overall, our findings established CPSF4 as a pro-tumorigenic factor in colorectal cancer progression, and suggested that targeting CPSF4-hTERT axis may represent a promising therapeutic strategy in colon cancer treatment.