PURα mediates epithelial-mesenchymal transition to promote esophageal squamous cell carcinoma progression by regulating Snail2

Esophageal squamous cell carcinoma (ESCC) is one of the most common lethal cancers in the world. Dysregulation of purine-rich element binding protein alpha (PUR alpha), which contributes to the initiation of PUR. syndrome, is reportedly involved in the progression of multiple cancers, but its function and underlying mechanisms in ESCC progression remain unclear. Here, we first demonstrated that PUR alpha promoted cell growth, migration and invasion in ESCC both in vitro and in vivo. An immunohistochemistry assay was then performed on 225 ESCC tissues, showing that high PUR alpha expression was positively associated with lymph node metastasis and the AJCC stage, and the ESCC patients with positive PURa expression had worse survival. In addition, RNA sequencing implied that PUR alpha induced epithelial-mesenchymal transition (EMT) in ESCC, which was further confirmed by qPCR, Western blotting and immunofluorescence analyses. Mechanistically, PUR alpha enhanced the transcription of Snail2 by binding to its promoter region. Knockdown of Snail2 reversed PUR alpha-induced EMT and inhibited the migration and invasion of ESCC cells. In conclusion, this study indicated that PUR alpha promotes Snail2 transcriptional activity to induce EMT during ESCC progression.

Automated summary

PUR alpha promotes cell growth, migration, and invasion in ESCC, likely through inducing EMT to contribute to the progression of ESCC. High expression of PUR alpha is associated with lymph node metastasis, advanced AJCC stage, and worse survival outcomes in ESCC patients.