SRSF9 (Serine And Arginine Rich Splicing Factor 9)

We critically appraise therapeutic innovations targeting aberrant splicing, including small molecule spliceosome modulators, antisense oligonucleotides like nusinersen, and CRISPR/dCas13-based RNA editing. By integrating molecular mechanisms with translational advances, this review provides a conceptual framework to accelerate RNA-targeted precision medicine in the era of spatial multiomics and artificial intelligence.

Loss of SRSF9 or antisense oligonucleotides-mediated isoform switch of NUMB mRNA inhibited OC growth in vitro and in vivo. In conclusion, this study reveals that SRSF9 condensation promotes OC progression through modulation of alternative splicing, in competition with m6A modification.

This metabolic reprogramming by BNIP3-Δ3 enhances breast cancer progression, including proliferation and invasion, and confers chemoresistance to paclitaxel. Collectively, our study identifies a previously unreported mechanism where SRSF9 governs the balance between autophagy and the Warburg effect via BNIP3 alternative splicing, thereby establishing a critical link between splicing regulation, metabolic adaptation, and therapeutic resistance in breast cancer.

This study elucidates the mechanism by which SRSF9 phase separation mediates splicing in oral cancer, thereby establishing a basis for considering SRSF9 and its associated SLC37A4-S isoforms as potential therapeutic targets for oral cancer treatment.

RNA pull-down, RNA immunoprecipitation (RIP), and actinomycin D experiments were performed to investigate the relationships between SRSF9 and USP22...SRSF9 enhanced the malignant characteristics of OC through a positive feedback loop of SRSF9/USP22/ZEB1. This functional circuit may help in the development of novel therapeutic approaches for treating OC.

Inhibition of the Cdc2-like kinase (CLK) family by the small molecules cirtuvivint or lorecivivint results in the decreased expression of ARV7. Both inhibitors show potent anti-proliferative effects in enzalutamide-treated or -naive PC models. Thus, targeting aberrant alternative splicing at the 3'UTR of ARV7 by disturbing the CLK2/SRSF9 axis might be a valuable therapeutic approach in late stage, ARSI-resistant PC.

Collectively our results underscore the critical involvement of SRSF family members in the context of oral cancer, highlighting their potential as key players in the altered splicing dynamics associated with cancer progression.

These findings uncover the cellular function of SRSF9 in GBM and highlight its therapeutic potential for GBM.

EEF1D knockdown reversed the malignant phenotype induced by SRSF9 overexpression. These findings demonstrated that EEF1D promotes CRC progression, and EEF1D may be a molecular target against CRC.

In vivo experiments demonstrated that AXIN1-L inhibited HCC metastasis, whereas SRSF9 promoted HCC metastasis in part by regulating the level of AXIN1-S. AXIN1, a tumor suppressor protein that targets the AXIN1/Wnt/β-catenin signaling axis, may be a promising prognostic factor and a valuable therapeutic target for HCC.

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.

Cisplatin-induced exosomes transfer PANDAR and lead to a rapid adaptation of OC cell survival through accumulating SRSF9 following cisplatin stress exposure.