Fusobacterium nucleatum promotes colorectal cancer metastasis by modulating KRT7-AS/KRT7
Fusobacterium nucleatum promotes colorectal cancer metastasis by modulating KRT7-AS/KRT7
复制标题
具核梭杆菌通过调节KRT7-AS/KRT7促进结直肠癌转移
DOI：
10.1080/19490976.2019.1695494
复制
发表时间：
2020-01-10
期刊：
影响因子：
12.2
通讯作者：
Wang, Liangjing
中科院分区：
文献类型：
--
作者：
Chen, Shujie;Su, Tingting;Wang, Liangjing
CRC 患者中已发现具核梭杆菌 (Fn) 富集，且与较差的预后相关。然而，Fn是否参与CRC的转移尚不清楚。在这里，我们发现有淋巴结转移的CRC患者中Fn的丰度显着增加。为了进一步阐明Fn在CRC转移中的作用，我们在孵育具有或不具有Fn的CRC细胞系并通过尾静脉将Fn处理或未处理的CRC细胞注射到裸鼠体内后进行transwell和伤口愈合测定。结果表明，Fn感染促进CRC细胞体外迁移，以及体内肺转移。有趣的是，通过荧光原位杂交检测到裸鼠肺转移病灶中 Fn 的定植。从机制上讲，RNA 测序和验证研究表明，Fn 显着上调 CRC 细胞中长非编码 RNA Keratin7 反义 (KRT7-AS) 和 Keratin7 (KRT7) 的表达。重要的是，Fn 诱导的 CRC 肺转移因 KRT7-AS 的消耗而减弱。此外，KRT7-AS 通过上调 KRT7 促进 CRC 细胞迁移。随后，我们发现NF-kappa B信号通路参与了Fn感染后KRT7-AS的上调。总之，Fn感染通过激活NF-kappa B通路上调KRT7-AS/KRT7，促进CRC细胞体外迁移和体内转移。
The enrichment of Fusobacterium nucleatum (Fn) has been identified in CRC patients and associated with worse outcomes. However, whether Fn was involved in the metastasis of CRC was not well determined. Here, we found that the abundance of Fn was significantly increased in CRC patients with lymph nodes metastasis. To further clarify the role of Fn in CRC metastasis, we performed transwell and wound healing assays after incubating CRC cell lines with or without Fn and injected Fn-treated or untreated CRC cells into nude mice via tail vein. The results indicated that Fn infection promoted CRC cells migration in vitro, as well as lung metastasis in vivo. Interestingly, colonization of Fn was detected in metastatic lung lesions of nude mice by fluorescence in situ hybridization. Mechanistically, RNA sequencing and validation study revealed that Fn significantly upregulated the expression of long non-coding RNA Keratin7-antisense (KRT7-AS) and Keratin7 (KRT7) in CRC cells. Importantly, Fn-induced CRC lung metastasis was attenuated by the depletion of KRT7-AS. In addition, KRT7-AS facilitated CRC cells migration by upregulating KRT7. Subsequently, we found that NF-kappa B signaling pathway was involved in the upregulation of KRT7-AS upon Fn infection. In conclusion, Fn infection upregulated KRT7-AS/KRT7 by activating NF-kappa B pathway, which promoted CRC cell migration in vitro and metastasis in vivo.