Comprehensive Genomic Profiling Identifies as a Negative Regulator of EMT, CTCs, and Metastasis of Hepatocellular Carcinoma.

BACKGROUND

FAT atypical cadherin 1 () acts as a tumor suppressor or oncogene, which regulates cell adherence, proliferation, motility, and actin kinetics. gene expression is closely related to hepatocarcinogenesis; however, the function and mechanism of in hepatocellular carcinoma (HCC) remain unclear.

METHODS

Here, we screened for the , which is intimately linked to the development and progression of HCC, both in circulating tumor cells (CTCs) and tumor tissues using next generation sequencing (NGS). Immunohistochemical staining was performed to detect FAT1 protein expression. To determine the impact of on epithelial-mesenchymal transition (EMT), migration and invasion of HCC, an in vitro transwell assay and Western blot were performed. Moreover, Gene Set Enrichment Analysis was carried out to discover the underlying mechanism. Finally, animal experiments were conducted to confirm the effects of on HCC metastasis and tumorigenicity.

RESULTS

Our results showed that expression was decreased in HCC tissues, while in vitro and in vivo, the knockdown facilitated invasion, cell motility, colony formation, and proliferation. knockdown also resulted in decreased expression of E-cadherin and markedly elevated expression of N-cadherin, vimentin, and snail. We also confirmed our hypothesis from the analysis of group differences in the CTC phenotype and lung metastasis in nude mice.

CONCLUSION

Our findings illustrated that played a negative regulatory role in the HCC EMT and metastasis, providing further evidence for the role played by in the formation and progression of HCC.