Minor intron splicing is critical for survival of lethal prostate cancer.

The evolutionarily conserved minor spliceosome (MiS) is required for protein expression of ∼714 minor intron-containing genes (MIGs) crucial for cell-cycle regulation, DNA repair, and MAP-kinase signaling. We explored the role of MIGs and MiS in cancer, taking prostate cancer (PCa) as an exemplar. Both androgen receptor signaling and elevated levels of U6atac, a MiS small nuclear RNA, regulate MiS activity, which is highest in advanced metastatic PCa. siU6atac-mediated MiS inhibition in PCa in vitro model systems resulted in aberrant minor intron splicing leading to cell-cycle G1 arrest. Small interfering RNA knocking down U6atac was ∼50% more efficient in lowering tumor burden in models of advanced therapy-resistant PCa compared with standard antiandrogen therapy. In lethal PCa, siU6atac disrupted the splicing of a crucial lineage dependency factor, the RE1-silencing factor (REST). Taken together, we have nominated MiS as a vulnerability for lethal PCa and potentially other cancers.

Healthcare Resource Utilization and Costs Associated With Eosinophilic Esophagitis Among Commercially Insured Patients in the United States.

INTRODUCTION: To evaluate real-world healthcare resource utilization (HCRU) and costs associated with eosinophilic esophagitis (EoE) in the United States. METHODS: Retrospective case-control cohort analysis of Optum Clinformatics claims data (January 2008-September 2020) comparing unadjusted and adjusted HCRU (visits per 1,000 patients per month) and all-cause costs (per patient per month). RESULTS: Patients with EoE incurred significantly higher monthly HCRU (adjusted Δ [95% confidence interval]: inpatient visits, 2.8 [0.1-4.0]; emergency department visits, 14.7 [4.3-32.1]; outpatient visits, 388.8 [362.1-418.0]); and costs ($581 [$421-$600]) vs matched controls (all P < 0.001). DISCUSSION: EoE imposes substantial economic burden. More effective and targeted treatments that improve outcomes for patients are needed.