Periodic tryptophan protein 1 promotes colorectal cancer growth via ribosome biogenesis.

Abstract

Background: Periodic tryptophan protein 1 (PWP1) is a member of the WD-40 family, located at the nucleus. The study of PWP1 in malignant tumors is at the initial stage. Its role and mechanism in colorectal cancer (CRC) remain unclear.

Methods: KEGG pathway analysis were used for bioinformatics analysis. The protein expression of PWP1 in the tissue microarrays was detected by immunohistochemical methods. Colony and CCK-8 were used for PWP1 function in vitro, and the orthotopic model was used to assess PWP1 function in vivo. The growth of CRC was tracked by the Living Imaging System. Immunofluorescence was used for the quantification of nascent rRNAs. Polysome fractionation analysis was used to detect mRNA abundance.

Results: GEO database was used to identify differential genes with elevated expression in CRC and followed by a KEGG analysis, which revealed that the ribosome synthesis pathway was enriched in CRC, with PWP1 displaying the most significant differential expression. Subsequently, the results of both in vitro and in vivo experiments demonstrated that PWP1 knockdown inhibited the proliferation of CRC. The results of immunofluorescence demonstrated that PWP1 knockdown suppressed de novo rRNA synthesis. Then, the differential proteins were examined, and this revealed that the most significantly downregulated proteins were those associated with DNA replication and mismatch repair functions following PWP1 interference. Moreover, ribosome profiling demonstrated significant downregulation of mRNAs associated with above functions.

Conclusion: We found that the PWP1-ribosome synthesis pathway is instrumental in achieving precise regulation of downstream signaling pathways, which in turn promote CRC growth.