ABSTRACT
Almost 50% myelodysplastic syndromes (MDS) patients have different splicing factor mutations, including SF3B1, SRSF2, U2AF1. Different splicing factor mutations cause the various mechanisms of slicing abnormality and eventually lead to the similar MDS phenotypes, indicating that splicing factor mutations might generate the common pathopoiesia pathway different from slicing abnormality. Recent studies have shown that SF3B1, U2AF1 and SRSF2 mutations could contribute to the accumulation of R-loop, cause DNA damage and repair abnormality, activate ATR-Chk1 pathway and finally promote apoptosis and tumorigenesis. This paper reviews the role of R-loop in the pathogenesis of MDS and the progress of related targeted drugs.
ABSTRACT
Objective:To explore the predictive effect of alternative splicing events and splicing factors on the prognosis of prostate cancer patients with androgen deprivation therapy (ADT).Methods:The relevant clinical and transcriptome information of 60 prostate cancer patients with ADT were downloaded from TCGA database, and the alternative splicing events information was obtained. LASSO and Cox regression models were used to screen the relevant alternative splicing events and splice factors through R language package. The related model was established, and the independent prognostic analysis and related regulatory network analysis were performed.Results:A total of 44 070 associated alternate splicing events were identified in prostate cancer patients, including 3 525 alternate acceptor sites (AA), 3 101 alternate donor sites (AD), 9 035 alternate promoters (AP), 8 663 alternate terminators (AT), 16 772 exon skipping (ES), 228 exon mutual exclusion (ME), and 2 747 retained intron (RI). Through univariate Cox proportional hazard regression model, 1 349 alternate splicing events were identified as disease-free survival-related splicing events (DFS-SE) related to ADT, including 145 AA events, 102 AD events, 243 AP events, 189 AT events, 557 ES events, 6 ME events, and 107 RI events. Multivariate Cox regression analysis show that after adding clinical related information, ME events (ANK3|11852|ME, TCF7L2|151705|ME, UBR2|127390|ME and SLC39A14|140283|ME) may be independent prognostic factors for predicting ADT resistance ( HR = 1.398, 95% CI 1.156-1.689, P<0.01). Conclusion:The combination of ME-type alternate splicing events and related clinical data has certain significances in predicting the effectiveness of ADT in prostate cancer patients, and plays an important role in the research on the resistance of prostate cancer patients to ADT.
ABSTRACT
PURPOSE: Splicing factors play important roles in tumorigenesis. Serine/arginine-rich splicing factors 2 (SRSF2) and SRSF4 proteins, the members of SR family proteins, are dysregulated in various cancers. However, their protein expression levels and diagnostic values are unclear in colorectal cancer.METHODS: We quantified the protein levels of SRSF2, SRSF4, and previously known colon cancer markers (heterogeneous nuclear ribonucleoprotein A1 [HNRNPA1] and carcinoembryonic antigen [CEA]) in tumor compared with adjacent normal-looking areas (non-tumor) of the colon in Korean patients with colon cancer using immunoblot analysis.RESULTS: The protein levels of HNRNPA1 and CEA were remarkably increased in tumor compared to non-tumor tissue and up-regulated in all of the tumor samples. However, the protein levels of SRSF2 and SRSF4 in tumor tissue were reduced in contrast with those of non-tumor tissue.CONCLUSION: None of the SRSF proteins were significantly different between the low (≤II) and high (>II) stages.