LncRNA SNHG16 facilitates the liver metastasis of colorectal cancer by modulating circulating tumor cell epithelial-mesenchymal transition via a positive feedback loop with the YAP1/TEAD1 complex

Abstract Background: 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 molecular mechanism of CTC EMT remains largely unknown. Results: Here, we studied the oncogenic long noncoding RNA (lncRNA) SNHG16, whose expression is correlated with advanced TNM stage, distant metastasis, and a poor prognosis in CRC patients. Furthermore, loss- and gain-of function revealed that SNHG16 promoted CRC proliferation, migration, invasion, EMT, mesenchymal-type CTC (MCTC) generation, and liver metastasis through YAP1. Mechanistically, SNHG16 could act as a miRNA sponge to sequester miR-195-5p on Ago2, thereby protecting YAP1 from repression. Moreover, YAP1 could combine with TEA domain transcription factor 1 (TEAD1) to form a YAP1/TEAD1 complex, which could in turn bind to the promoter of SNHG16 and regulate its transcription. Finally, we demonstrated that YAP1 significantly promoted tumor progression, and that SNHG16 rescued the effect of YAP1 on tumor progression. Conclusion: Herein, we clarified a hitherto unexplored SNHG16-YAP1/TEAD1 positive feedback loop, which may be a candidate target for CRC treatment.