FAST1 Predicts Poor Survival of Renal Carcinoma and Promotes Its Progression Through the TGF-β/Smad Pathway

Purpose: Renal carcinoma (RC) originates in the renal tubular epithelial system, among which renal cell carcinoma (RCC) is the most frequent one. The forkhead activin signal transducer 1 (FAST1) has been shown to interfere with tumor progression as an oncogene, while its role in RC is limited. Therefore, this paper explored the prognostic significance, specific effects, and related mechanisms of FAST1 on RC. Patients and Methods: Cell colony formation assay, cell counting kit-8 (CCK8) assay, flow cytometry and Transwell assay were used to test cell proliferation, viability, apoptosis, migration and invasion, respectively. Western blot (WB) was employed to determine the protein level of FAST1. Results: Our study confirmed that FAST1 was up-regulated in RC tissues and cell lines, and its overexpression often represented a poor prognosis of RC patients. Meanwhile, the in vitro experiments showed that overexpressing FAST1 facilitated RC cell viability, proliferation, migration, invasion and epithelial-mesenchymal transition (EMT), and repressed cell apoptosis. In addition, the in vivo experiments illustrated that the up-regulation of FAST1 strengthened tumor growth. On the contrary, knocking down FAST1 had the opposite effects. Mechanistically, The TGF-beta/Smad pathway contributed to RC evolvement and was activated by FAST1 both in vitro and in vivo. Conclusion: This article suggests that FAST1 exerts a carcinogenic role in RC by regulating the TGF-beta/Smad signaling.

Automated summary

The study confirmed that FAST1 is up-regulated in RC tissues and cell lines, and its overexpression indicates a poor prognosis for RC patients. Overexpressing FAST1 promoted RC cell viability, proliferation, migration, invasion, and EMT, while repressing apoptosis. Mechanistically, FAST1 regulates RC progression through activation of the TGF-beta/Smad signaling pathway.