SRSF3 (Serine And Arginine Rich Splicing Factor 3)

Pathway analysis via the Kyoto Encyclopedia of Genes and Genomes (KEGG) highlighted critical signalling pathways involved in CCa oncogenesis. In conclusion, theophylline demonstrates cytotoxicity in CCa cells, suggesting its potential for repurposing in CCa theranostics, though further optimization is necessary.

Our work uncovers a novel function of AFAP1-AS1 in regulating RNA alternative splicing through the modulation of splicing factors phase separation. This mechanism highlights an unrecognized pathway by which AFAP1-AS1 promotes drug resistance in lung adenocarcinoma, suggesting that AFAP1-AS1 and its regulated splicing events may serve as potential biomarkers or therapeutic targets for the treatment of lung adenocarcinoma.

Among these, stemness, therapeutic resistance, EMT, and senescence are the most prominently regulated via AS regulatory axis. Finally, the clinical opportunities of AS as a biomarker and prognostic indicator, alongside its therapeutic promises is discussed with particular emphasis on targeting splicing regulators to disrupt cancer-specific splicing events, offering promising avenues for the development of novel and effective cancer treatments.

We also generated SRSF3 siRNA-encapsulating lipid nanoparticles as a future therapeutic tool. This study proposes a therapeutic strategy for NSCLC that is independent of the mutation status of TP53 and TK-encoding genes.

Further analysis revealed that arginine may disrupt the interaction between ribosomal protein S3 (RPS3) and serine/serine and arginine rich splicing factor 3 (SRSF3), thereby further suppressing the expression of apoptosis-related proteins induced by S. Tm. Our research offers new targets and approaches for treating bacterial infection-induced intestinal inflammation.

In combination with eCLIP, we confirmed that ORF57 directly binds to an AU-rich RNA motif, which may enable ORF57 to discriminate viral from cellular RNAs based on the nucleotide bias of KSHV lytic RNAs. In addition, we captured the RBPome of two ORF57-dependent viral transcripts and identified the host RNA processing factor SRSF3 as a key regulator of viral replication.

Mechanistically, NXF1 interferes with the binding of SRSF3 to exon 3 of SP4, preventing the formation of the "cancerous" long SP4 isoform (L-SP4) and promoting the "noncancerous" short SP4 isoform (S-SP4), which lacks the transactivation domain. In conclusion, NXF1 suppresses ECa tumorigenicity and progression through an SRSF3-mediated SP4 alternative splicing mechanism, and could serve as a novel prognostic biomarker for clinical intervention in ECa.

Interestingly, we also found that SRSF3 can undergo phase separation and promotes proliferation of lung cancer cells. These results suggest that SRSF3 may serve as a potential target for the diagnosis and treatment of lung cancer.

This study suggests a therapeutic strategy for NSCLC irrespective of the mutation status of TP53 and TK-encoding genes. Knockdown of a splicing factor SRSF3 increases cellular senescence in NSCLC cells including those with no targetable mutation of tyrosine kinases and thus may represent a novel therapeutic strategy for a hard-to-treat group of NSCLC.

Moreover, Srsf3 KO suppresses the expression of ERα and Foxa genes to reduce Lifr and Egfr but induce Myc expression and promote liver cancer in female mice. Together, our data highlight a new functional paradigm of SRSF3 at its physiological level in tissue context-dependent gene regulation.

Finally, we demonstrated that the SARS-CoV-2 N protein enhances the antitumor effects of etoposide in xenograft tumor mouse model. These findings reveal a novel antitumor mechanism of the SARS-CoV-2 N protein, positioning it as a potential therapeutic agent for lung cancer patients.

These findings show that TTK plays a key role in maintaining mitophagy in BC cells. Targeting TTK could offer a promising new approach for BC treatment by disrupting mitophagy and inducing mitochondrial apoptosis.