Int J Biol Sci 2022; 18(14):5291-5308. doi:10.7150/ijbs.73438 This issue Cite

Research Paper

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

Zhenxian Xiang1,2,3,4*, Guoquan Huang6,2,3,4*, Haitao Wu2,3,4,5*, Qiuming He1,2,3,4, Chaogang Yang1,2,3,4, Rongzhang Dou1,2,3,4, Qing Liu1,2,3,4, Jialing Song1,2,3,4, Yan Fang1,2,3,4, Shuyi Wang1,2,3,4✉, Bin Xiong1,2,3,4✉

1. Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, No.169 Donghu Road, Wuchang District, Wuhan, 430071, China.
2. Department of Gastric and Colorectal Surgical Oncology, Zhongnan Hospital of Wuhan University, No.169 Donghu Road, Wuchang District, Wuhan, 430071, China.
3. Hubei Key Laboratory of Tumor Biological Behaviors, No.169 Donghu Road, Wuchang District, Wuhan, 430071, China.
4. Hubei Cancer Clinical Study Center, No.169 Donghu Road, Wuchang District, Wuhan, 430071, China.
5. Department of Thyroid and Breast Surgery, Maternal and Child Hospital of Hubei Province, Wuhan, 430071, People's Republic of China.
6. Department of Gastrointestinal Surgery, Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, China.
*These authors have contributed equally to this work.

Citation:
Xiang Z, Huang G, Wu H, He Q, Yang C, Dou R, Liu Q, Song J, Fang Y, Wang S, Xiong B. 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. Int J Biol Sci 2022; 18(14):5291-5308. doi:10.7150/ijbs.73438. https://www.ijbs.com/v18p5291.htm
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Abstract

Graphic abstract

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.

Keywords: SNHG16, YAP1, TEAD1, CTCs, EMT


Citation styles

APA
Xiang, Z., Huang, G., Wu, H., He, Q., Yang, C., Dou, R., Liu, Q., Song, J., Fang, Y., Wang, S., Xiong, B. (2022). 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. International Journal of Biological Sciences, 18(14), 5291-5308. https://doi.org/10.7150/ijbs.73438.

ACS
Xiang, Z.; Huang, G.; Wu, H.; He, Q.; Yang, C.; Dou, R.; Liu, Q.; Song, J.; Fang, Y.; Wang, S.; Xiong, B. 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. Int. J. Biol. Sci. 2022, 18 (14), 5291-5308. DOI: 10.7150/ijbs.73438.

NLM
Xiang Z, Huang G, Wu H, He Q, Yang C, Dou R, Liu Q, Song J, Fang Y, Wang S, Xiong B. 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. Int J Biol Sci 2022; 18(14):5291-5308. doi:10.7150/ijbs.73438. https://www.ijbs.com/v18p5291.htm

CSE
Xiang Z, Huang G, Wu H, He Q, Yang C, Dou R, Liu Q, Song J, Fang Y, Wang S, Xiong B. 2022. 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. Int J Biol Sci. 18(14):5291-5308.

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