ArticleJournal of translational medicine2026
Pharmacological targeting of SF3a1-MDM4 splicing vulnerability in ovarian cancer with rifaximin and antisense oligonucleotide.
Article in Journal of translational medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
Abstract
backgroundOvarian cancer (OC) is the most deadly gynecological malignancy, mainly due to insufficient studies on its mechanisms and lack of effective therapies. Alternative splicing (AS) dysregulation has deepened understanding of cancer pathogenesis. As a constitutive molecular consisting spliceosome, the pathogenesis and therapeutic potential of SF3a1 in solid tumors are rarely studied.
methodsThe expressions and prognostic values of SF3a1 were accessed using bioinformatics. The functions of SF3a1 were evaluated using gain- and loss-of-function strategies. Whole transcriptome sequencing and mass spectrometry analysis were conducted to capture signaling axis of SF3a1. Semi-qPCR, qRT–PCR, WB, IHC and rescue experiments were exploited to validate the sequencing results. Targeted antisense oligonucleotide (ASO) was designed and its treatment efficacy was verified. Virtual screening was used to identify small molecule inhibitor of SF3a1, whose therapeutic potential on OC was evaluated via in vitro and in vivo assays.
resultsThis study found SF3a1 played an indispensable role in OC pathogenesis. SF3a1 knockdown impaired malignant behaviors and reprogrammed splicing landscape of OC cells. Skipped exon (SE) event of MDM4-exon6 (exon7 in mouse) increased, leading to formation of MDM4-short (MDM4-s) isoform, which was subsequently degraded. Total MDM4 level was therefore downregulated, leading to P53 pathway activation and OC inhibition. Additionally, ASO targeting MDM4 pre-mRNA sequence bound by SF3a1 mimicked the alternative regulation caused by SF3a1 knockdown, and showed significant inhibitory effect on OC proliferation. Rifaximin, identified as an inhibitor targeting SF3a1, effectively killed OC cells and enhanced cisplatin’s efficacy in combination therapy. Moreover, CDK6 was found to phosphorylate SF3a1 at S359, which decreased its protein half-life and influenced downstream MDM4 splicing.
conclusionsOur findings uncover the oncogenic impact of SF3a1 in OC and highlight the prospects to target it by rifaximin and downstream MDM4 AS by ASO, synergistically improving the therapeutic effectiveness of cisplatin in OC.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.