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

Med Oncol. 2023 Sep 1;40(10):288. doi: 10.1007/s12032-023-02157-9.

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.

Keywords: Esophageal cancer; RIG-I; Ubiquitination; p21.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Esophageal Neoplasms* / pathology
  • Esophageal Squamous Cell Carcinoma* / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice
  • Mice, Nude

Substances

  • RIGI protein, human