SNHG16 upregulation-induced positive feedback loop with YAP1/TEAD1 complex in Colorectal Cancer cell lines facilitates liver metastasis of colorectal cancer by modulating CTCs epithelial-mesenchymal transition.
SNHG16 upregulation-induced positive feedback loop with YAP1/TEAD1 complex in Colorectal Cancer cell lines facilitates liver metastasis of colorectal cancer by modulating CTCs epithelial-mesenchymal transition.
复制标题
结直肠癌细胞系中 SNHG16 上调诱导的 YAP1/TEAD1 复合物正反馈环通过调节 CTC 上皮间质转化促进结直肠癌肝转移
DOI：
10.7150/ijbs.73438
复制
发表时间：
2022
影响因子：
9.2
通讯作者：
Xiong, Bin
中科院分区：
文献类型：
--
作者：
Xiang, Zhenxian;Huang, Guoquan;Wu, Haitao;He, Qiuming;Yang, Chaogang;Dou, Rongzhang;Liu, Qing;Song, Jialing;Fang, Yan;Wang, Shuyi;Xiong, Bin
循环肿瘤细胞（CTC）是结直肠癌（CRC）转移的重要前体细胞。上皮-间充质转化（EMT）过程通过允许这些细胞逃避抗转移检查点以介导远处转移而促进CTC侵袭。然而，肿瘤EMT的具体分子机制仍不清楚。在我们之前对YAP 1通路的研究基础上，我们进一步研究了上游分子小核仁RNA宿主基因16（SNHG 16），其表达与CRC患者的晚期TNM分期、远处转移和预后不良相关。此外，功能丧失和获得测定显示SNHG 16通过YAP 1促进CRC集落形成、增殖、迁移、侵袭、EMT、间充质样CTC产生和肝转移。SNHG 16作为miRNA海绵，将miR-195- 5 p隔离在Ago 2上，从而保护YAP 1不受抑制。此外，YAP 1结合TEA结构域转录因子1（TEAD 1）形成YAP 1/TEAD 1复合物，该复合物进而结合SNHG 16启动子中的两个位点并调节SNHG 16的转录。最后，体内实验表明，SNHG 16的抑制抑制了肿瘤进展，并且YAP 1挽救了SNHG 16对肿瘤进展的作用。在此，我们已经阐明了迄今为止尚未探索的SNHG 16-YAP 1/TEAD 1正反馈环，这可能是CRC治疗的候选靶点。
Circulating tumor cells (CTCs) are important precursors of colorectal cancer (CRC) metastasis. The epithelial-mesenchymal transition (EMT) process facilitates CTC invasion by allowing these cells to evade antimetastatic checkpoints to mediate distant metastasis. However, the specific molecular mechanism of tumor EMT remains largely unknown. Based on our previous research on the YAP1 pathway, we further studied the upstream molecule small nucleolar RNA host gene 16 (SNHG16), whose expression was correlated with advanced TNM stage, distant metastasis, and poor prognosis in CRC patients. Furthermore, loss- and gain-of-function assays revealed that SNHG16 promoted CRC colony formation, proliferation, migration, invasion, EMT, mesenchymal-like CTC generation, and liver metastasis through YAP1. Mechanistically, SNHG16 acted as a miRNA sponge to sequester miR-195-5p on Ago2, thereby protecting YAP1 from repression. Moreover, YAP1 bound TEA domain transcription factor 1 (TEAD1) to form a YAP1/TEAD1 complex, which in turn bound two sites in the promoter of SNHG16 and regulate SNHG16 transcription. Finally, in vivo experiments showed that the inhibition of SNHG16 suppressed tumor progression, and that YAP1 rescued the effect of SNHG16 on tumor progression. Herein, we have clarified a hitherto unexplored SNHG16-YAP1/TEAD1 positive feedback loop, that may be a candidate target for CRC treatment.
登录
查看更多内容
starBase v2.0：从大规模 CLIP-Seq 数据中解码 miRNA-ceRNA、miRNA-ncRNA 和蛋白质-RNA 相互作用网络
影响因子：
14.9
作者：
Li JH;Liu S;Zhou H;Qu LH;Yang JH
通讯作者：
Yang JH
影响因子：
37.3
作者：
Dong, Huaying;Hu, Jianguo;Han, Mingli
通讯作者：
Han, Mingli
影响因子：
11.1
作者：
Joosse SA;Gorges TM;Pantel K
通讯作者：
Pantel K
影响因子：
2.9
作者：
Abylkassov R;Xie Y
通讯作者：
Xie Y
影响因子：
4.8
作者：
Dong, Aiwen;Gupta, Aparna;Lowe, Anson W.
通讯作者：
Lowe, Anson W.