RIG-I promotes cell proliferation in esophageal squamous cell carcinoma by facilitating p21 degradation.

ABSTRACT

Retinoic acid-inducible gene-I (RIG-I) is considered a key sensor for host recognition of RNA virus infections. Recent studies have shown that RIG-I also regulates carcinogenesis. However, the role of RIG-I in esophageal squamous cell carcinoma (ESCC) remains unclear. We investigated the RIG-I expression in ESCC cells using a public database, immunohistochemistry, and Western blotting. We evaluated the proliferative activity of ESCC cells using CCK-8, colony formation, and EdU staining assays. Further, we determined the ESCC cell-cycle changes using flow cytometry and the ubiquitination of p21 in the cells using cycloheximide chase and ubiquitination assays. Finally, we verified the in vivo effects of RIG-I on ESCC cells by constructing xenograft models. RIG-I was highly expressed in ESCC cells and significantly promoted their proliferation and cell-cycle. Moreover, RIG-I knockdown inhibited xenograft growth in nude mice. Furthermore, RIG-I accelerated the cell-cycle by promoting the ubiquitination and degradation of p21. Overall, this study revealed that the increased expression of RIG-I due to ESCC accelerated the progression of esophageal cancer by promoting the ubiquitination and degradation of p21, which is related to the prognosis of ESCC. Thus, RIG-I may be a novel therapeutic target for ESCC treatment.