PRPF8 (Pre-MRNA Processing Factor 8)

Moreover, we demonstrate that the spliceosome activity inhibition using pladienolide-B in primary patient´s derived cell-cultures might serve as a potential therapeutic tool worth to be explored in humans. Altogether, our results demonstrate a drastic and clinically relevant spliceosome-associated molecular dysregulation in craniopharyngiomas, which could serve as a potential source of novel diagnostic/prognostic biomarkers and therapeutic targets.

Besides, the association of ERCC1 splicing isoforms with cGAS/STING signaling in cisplatin-treated cells was analyzed, and the modulation of PRPF8 on ERCC1 exon skipping splicing was elucidated by RNA immunoprecipitation...Mechanistically, PRPF8 was identified to be directly interacted with modulating ERCC1 exon 3 skipping, while β-elemene was found to be involved in the activation of cGAS-STING signaling as an inhibitor of PRPF8. Our data reveal that the ERCC1 exon 3 skipping isoform is associated with DDR and the cGAS/STING innate immune pathway, which provide preclinical rationale for using alternative or complement immunotherapy in Platinum-sensitive NSCLC patients.

Furthermore, we examine the molecular pathways associated with PRPF8 dysregulation and their impact on cancer progression. We also discuss the emerging potential of targeting PRPF8 in cancer therapy, highlighting challenges in drug development.

Here, we utilize both bacterial infection and a synthetic colibactin analog to identify genes directly involved in colibactin response. These findings provide insight into how differences in gene expression may render certain individuals more vulnerable to colibactin-initiated tumor formation after DNA damage.

Finally, the in vitro pharmacological inhibition of splicing machinery using pladienolide B decreased aggressiveness features in all the BCa cell lines, showing a subtype-independent inhibitory potential, but being relatively innocuous in normal-like breast cells. These results demonstrate the profound dysregulation of the splicing machinery in BCa and their potential as source of promising diagnosis/prognosis markers, as well as valuable therapeutic targets for BCa.

ZNF649-AS1 promoted trastuzumab resistance and TAM-dependent PD-L1 expression in HER2-positive BC via promoting alternative splicing of EXOC7 by PRPF8.

In conclusion, the evaluation of an adolescent with profound long-term hypophosphatemia revealed a pituitary developmental defect associated with a stop gain variant in PRPF8. Hypophosphatemia alleviated with GH treatment. The pathological PRPF8 variant may contribute to abnormal pituitary development; however, its role in phosphate metabolism remains uncertain.

Providing evidence of clonality, somatic mutations were noted frequently in TN MPNs. Most of the genes involved are the ones related to epigenetic regulations and splicing. The average number of mutated genes per case was significantly higher in TN PMF as compared to TN ET.

Experimental modulation of these splicing factors in pancreatic cancer cell lines reverted their expression to non-tumor levels and resulted in decreased key tumor-related features. These results provide evidence that the splicing machinery is altered in PDAC, wherein PRPF8 and RBMX emerge as candidate actionable therapeutic targets.

In this review, we discuss aberrant splicing events induced by mutations affecting SFs (SF3B1, U2AF1, SRSR2, and ZRSR2), spliceosome components (PRPF8, LUC7L2, DDX41, and HNRNPH1), and epigenetic modulators (IDH1 and IDH2). Finally, we provide an extensive overview of the biological relevance of aberrant isoforms of genes involved in the regulation of apoptosis (e. g. BCL-X, MCL-1, FAS, and c-FLIP), activation of key cellular signaling pathways (CASP8, MAP3K7, and NOTCH2), and cell metabolism (PKM).

These findings provide insights into the molecular mechanisms underlying the therapeutic selection and reactivation of dormant cancer cells. This discovery opens a potential avenue for the development of therapeutic strategies aimed at preventing cancer recurrence following chemotherapy.

These results provide primary evidence for dysregulation of the splicing machinery in lung carcinoids and suggest a plausible functional role and therapeutic targetability of NOVA1, PRPF8 and SRSF10.