NXF1 (Nuclear RNA Export Factor 1)

These findings provide quantitative evidence supporting the biological and clinical relevance of the prioritized genes, and the five untargeted genes emerge as strong candidates for future experimental validation through CRISPR-based perturbation, gene silencing, and functional phenotypic assays. Overall, this integrative TOPSIS-network framework offers a robust and reproducible strategy for uncovering both established and novel therapeutic targets, expanding the landscape for precision oncology.

Owing to their fast replication and to the high error rate of their polymerases, viruses, particularly RNA viruses are prone to acquire SLiMs that mimic cellular SLiMs and thereby interfere with host cell signaling. In this work, we show that the leader (L) protein expressed by some cardioviruses (Picornaviridae family) uses two SLiMs in combination, which are individually shared by other pathogens: the first one, described previously, enables the L protein to hijack cellular kinases named RSKs, and the second one described in this work enables the L-RSK complex to target proteins RAE1 and NUP98 in the nuclear pore complex.

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.

In summary, our findings indicate that artificially synthesized MIR4726EccDNA is functional in cells and that MIR4726EccDNA enhances tumor progression and partially mediates drug resistance by enhancing MIR4726-5p/NXF1/NKIRAS2 axis dependent autophagy.

Our study demonstrates the utility of drug repositioning for identifying potential therapeutics for digestive system cancers. Amonafide and BX795 emerged as promising candidates in targeting both CRC and LIHC. Further in vivo studies and clinical trials are warranted to validate these findings.

Kaposi's sarcoma-associated herpesvirus (KSHV) globally disrupts host gene expression by inducing host shutoff which triggers a global repression of the host transcriptome via widespread RNA decay, RNA, nascent transcript hyperadenylation and nuclear export blocks, yet a subset of transcripts escape this repression. This study reveals that despite acquiring long poly(A) tails, select host mRNAs such as IL-6 evade nuclear retention by using the alternative CRM1-dependent export pathway and remain stable in the cytoplasm. These findings challenge the prevailing model that hyperadenylation alone dictates nuclear decay and uncover a selective mechanism by which crucial host transcripts bypass KSHV-mediated gene repression. Understanding this selective escape provides new insights into host-virus interactions and highlights CRM1 as a potential therapeutic target in KSHV-associated diseases.

Importantly, the expression level of NXF1 influences sensitivity to CDK12 inhibitors, which are emerging as novel anti-cancer drug candidates. This highlights the importance of considering the relationship between mRNA transcription and transport when targeting RNA transcription in cancer therapy.

Depletion of TERC hindered the assembly and subsequent nuclear localization of the telomerase complex, preventing TERT from functioning in telomere maintenance and transcription regulation. Our findings suggest that TERC is a potential biomarker for NSCLC diagnosis and prognosis and can be a target for NSCLC treatment.

HnRNPA2B1 knockdown or mRNA export inhibition can result in the retention of nuclear m6A-tagged mRNA associated with stemness maintenance, which suppresses BCSCs self-renewal and effectively improves the efficacy of doxorubicin therapy. These findings demonstrate the pivotal role of m6A-modified mRNA nuclear export in BC progression, highlighting that the inhibition of m6A-tagged mRNA and its nuclear export is a potential therapeutic strategy for the amelioration of cancer chemotherapy.

Importantly, several SRSF1 cancer-associated mutants fail to interact with FANCD2, leading to inefficient FANCD2 monoubiquitination, decreased mRNA export, and R-loop accumulation. We propose a model wherein SRSF1 and FANCD2 interaction links DNA damage response to the avoidance of pathogenic R-loops via regulation of mRNA export.

Fixed Duration of Venetoclax-Rituximab in Relapsed/Refractory Chronic Lymphocytic Leukemia Eradicates Minimal Residual Disease and Prolongs Survival: Post-Treatment Follow-Up of the MURANO Phase III Study. JCO 2019, 7(4):269-277

In this study, bicalutamide resistance genes and hub genes were identified in PCa, a risk model for predicting the prognosis of patients with PCa was constructed, and the tumor mutation heterogeneity and immune infiltration in high- and low-risk groups were analyzed. These findings offer new insights into ADT resistance targets and prognostic prediction in patients with PCa.