Inflammation plays a key role in the development of Colorectal Cancer (CRC), but the underlying regulatory mechanisms are yet to be fully elucidated. The K-homology splicing regulatory protein (KHSRP) is a multifunctional RNA-binding protein which regulates translation of transcripts containing ARE sequences in their 3’-UTR, affecting RNA fate at different levels. KHSRP has been implicated in different functions associated with cancer cell biology, such as inflammation and cell-fate determination. Importantly, KHSRP regulates expression of pro-tumorigenic and anti-inflammatory cytokines, potentially impacting on the tumor microenvironment. We have previously shown that knockdown of KHSRP expression in CRC cell lines regulates cell proliferation and clonogenic survival. KHSRP is also required for the secretion of the pro-angiogenic cytokines, IL-8 and VEGF, impacting on endothelial tube formation. To understand the global impact of KHSRP in regulation of CRC cell function we used Affimetrix Human Transcriptome array to investigate gene expression upon KHSRP silencing in SW480 CRC cells. A total of 210 genes were differentially expressed, 155 of which were up-regulated (100 coding and 55 non-coding genes) and 55 were down-regulated (34 coding and 21 non-coding genes). Among these were genes involved in RNA biology, inflammation, immunity, cell signaling and tumor-stroma interaction, shedding light on the potential mechanisms of action of KHSRP in epithelial cells. Representative targets have been selected for validation and further mechanistic studies. These data builds upon our previous findings suggesting a role for KHSRP in creating a tumor-permissive microenvironment in CRC.

Citation Format: Francesco Caiazza, Robert Power, Kate Killick, Des Higgins, Walter Kolch, Laura Breen, Sinead Aherne, Sudipto Das, Darran O’Connor, Miriam Tosetto, Blathnaid Nolan, David Fennelly, Kieran Sheahan, Glen Doherty, Elizabeth J. Ryan. The tumor-permissive role of KHSRP in colorectal cancer: Mechanistic insights from a gene expression study. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2878.