HuR is a ubiquitous nucleocytoplasmic RNA binding protein that exerts pleiotropic effects on cell growth and tumorigenesis. In this study, we explored the impact of conditional, tissue-specific genetic deletion of HuR on intestinal growth and tumorigenesis in mice. Mice lacking intestinal expression of HuR (Hur IKO mice) displayed reduced levels of cell proliferation in the small intestine and increased sensitivity to doxorubicin-induced acute intestinal injury, as evidenced by decreased villus height and a compensatory shift in proliferating cells. In the context of ApcMin mice, a transgenic model of intestinal tumorigenesis, intestinal deletion of the HuR gene caused a 3-fold decrease in tumor burden characterized by reduced proliferation, increased apoptosis and decreased expression of transcripts encoding anti-apoptotic HuR target RNAs. Similarly, Hur IKO mice subjected to an inflammatory colon carcinogenesis protocol (AOM-DSS administration) exhibited a 2-fold decrease in tumor burden. Hur IKO mice showed no change in ileal Asbt expression, fecal bile acid excretion or enterohepatic pool size that might explain the phenotype. Moreover, none of the HuR targets identified in Apc Min/+Hur IKO were altered in AOM-DSS treated Hur IKO mice, the latter of which exhibited increased apoptosis of colonic epithelial cells where elevation of a unique set of HuR-targeted pro-apoptotic factors was documented. Taken together, our results promote the concept of epithelial HuR as a contextual modifier of pro-apoptotic gene expression in intestinal cancers, acting independently of bile acid metabolism to promote cancer. In the small intestine, epithelial HuR promotes expression of pro-survival transcripts that support Wnt-dependent tumorigenesis, whereas in the large intestine epithelial HuR indirectly downregulates certain pro-apoptotic RNAs to attenuate colitis-associated cancer.

Obesity is associated with an increased risk of overall and pouch-related complications following IPAA. Obese patients should be counseled preoperatively about these risks accordingly.

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Patients who undergo neoadjuvant chemoradiation before rectal cancer surgery frequently have fewer than 12 lymph nodes harvested despite maintaining vigorous surgical standards. Lymph node ratios may provide excellent prognostic value and are possibly a better independent staging method than absolute positive lymph node counts when less than 12 lymph nodes are harvested after neoadjuvant treatment.