Forming cytoplasmic stress granules PURα suppresses mRNA translation initiation of IGFBP3 to promote esophageal squamous cell carcinoma progression

Esophageal squamous cell carcinoma (ESCC) is one of the most fatal malignancies worldwide. Recently, our group identified purine-rich element binding protein alpha (PUR alpha), a single-stranded DNA/RNA-binding protein, to be significantly associated with the progression of ESCC. Additional immunofluorescence staining demonstrated that PUR alpha forms cytoplasmic stress granules to suppress mRNA translation initiation. The expression level of cytoplasmic PUR alpha in ESCC tumor tissues was significantly higher than that in adjacent epithelia and correlated with a worse patient survival rate by immunohistochemistry. Functionally, PUR alpha strongly preferred to bind to UG-/U-rich motifs and mRNA 3 ' UTR by CLIP-seq analysis. Moreover, PUR alpha knockout significantly increased the protein level of insulin-like growth factor binding protein 3 (IGFBP3). In addition, it was further demonstrated that PUR alpha-interacting proteins are remarkably associated with translation initiation factors and ribosome-related proteins and that PUR alpha regulates protein expression by interacting with translation initiation factors, such as PABPC1, eIF3B and eIF3F, in an RNA-independent manner, while the interaction with ribosome-related proteins is significantly dependent on RNA. Specifically, PUR alpha was shown to interact with the mRNA 3 ' UTR of IGFBP3 and inhibit its expression by suppressing mRNA translation initiation. Together, this study identifies cytoplasmic PUR alpha as a modulator of IGFBP3, which could be a promising therapeutic target for ESCC treatment.

Automated summary

This study identifies cytoplasmic PUR alpha as a modulator of IGFBP3 in ESCC, affecting protein expression by suppressing mRNA translation initiation and significantly impacting patient prognosis. This suggests that cytoplasmic PUR alpha may serve as a promising therapeutic target for ESCC treatment.