Our findings identify the pro-tumorigenic property of the NSUN4/CDC20 cascade in NSCLC. Targeting the novel cascade may be a promising way for combating this deadly disease.

We report here that the cooperative binding of doxorubicin (Dox) with actinomycin D (ActD) enhances the specificity for consecutive GCCG sites in DNA. In vivo, the combination significantly suppresses tumor growth and outperforms the standard Dox and cyclophosphamide regimen in inhibiting metastasis. This study highlights targeting the activated EGFR pathway with sequence-specific DNA-targeting drug combinations as a potential TNBC treatment.

circKIAA1429 interacts with SETD1A to inhibit the enrichment of H3K4me3 and H3K27me3 on GLIS2 or NAP1L3 promoter, thus inhibiting/promoting the expression of GLIS2/NAP1L3 and accelerating the progression of HCC.

Overall, our study successfully established a combined therapeutic strategy using COR and PD-L1 inhibitors. This strategy has significant synergistic effects on cancer cells, highlighting its importance in cancer therapy.

EIF4E-mediated biogenesis of circPHF14 stabilizes WNT7A mRNA via interaction with PABPC1, which subsequently activates the Wnt/β-catenin pathway, promoting the growth and metastasis of PDAC. These findings indicate that circPHF14 holds promise as a biomarker and therapeutic target for PDAC.

IGF2BP1 stabilized AIFM2 mRNA to regulate ferroptosis and glycolysis and promoted HCC progression.

The characteristics of circ_ASH1L were determined by RNase R digestion, actinomycin D, and nucleo-plasmic separation assays...Similarly, modulation of CD36 expression efficiently counteracted the effect of miR-1254 on the malignant biological behavior of CC cells. In conclusion, circ_ASH1L promoted the malignant progression of CC via upregulating CD36 expression through sponging miR-1254.

The stability of circRNF20 was tested after treatment with actinomycin D. A nude mouse xenograft tumor model was established to validate the effect of IGF2BP2 in vivo...The overexpression of circRNF20 or CDCA4 abolished the inhibitory effect of IGF2BP2 silencing on BC cell proliferation. In conclusion, the binding of IGF2BP2 to circRNF20 prevents its degradation, thus facilitating BC cell proliferation via the HuR/CDCA4 axis.

The influence of METTL1 in m7G methylation and stability of RRP9 mRNA was evaluated by methylated immunoprecipitation (MeRIP) assay and Actinomycin D (Act D) treatment, respectively...METTL1 depletion impeded the growth of HCT-116 subcutaneous xenografts in vivo by RRP9. Our observations identified METTL1 as a crucial protumorigenic factor to drive growth, metastasis, and stemness of CRC cells through RRP9, offering new targets for combating CRC.

Taken together, our findings suggest that IGF2BP2 plays a critical role in regulating AR-V7 expression and stability, offering a novel target for developing therapeutic interventions for CRPC.

Combination testing with the conventional chemotherapeutic agents currently used to treat infants with ALL demonstrated additivity with cytarabine. Dactinomycin is extensively used for the treatment of solid tumors in children and has an acceptable safety profile when used to treat infants in this context. However, despite being readily translational and exhibiting promising in vitro cytotoxicity, dactinomycin showed limited efficacy in vivo and therefore does not represent a priority candidate for integrating into therapy for infants with ALL.

P4, N=100, Not yet recruiting, Boston Children's Hospital | Initiation date: Dec 2024 --> Dec 2025

Luciferase reporter, RNA immunoprecipitation, actinomycin D, and immunofluorescence assays were performed to investigate the molecule mechanisms of MFSD2A...Knockdown of MFSD2A abrogated the inhibitory effect of miR-3189-3p inhibitor on HCC cellular processes, and overexpression of MFSD2A reversed the tumor-promoting effect of HDLBP overexpression. Overall, MFSD2A exerts a tumor-inhibiting effect in HCC via suppression of TGF-β/Smad signaling, suggesting that MFSD2A may be a promising target for HCC therapy.

The findings of study reveal that METTL14-mediated m6A modification of LINC00340 exerts oncogenic function in RB via Notch signaling pathway, which may uncover a novel molecular mechanism driving RB progression and identify a potential therapeutic target for RB.

RNA pull-down, RNA immunoprecipitation, qRT-PCR, western blot, and actinomycin D assays were adopted to determine the relationships among LUCAT1, ALYREF, and TTYH3...TTYH3 overexpression eliminated the suppressive functions of ALYREF downregulation in NSCLC progression. LUCAT1 promotes TTYH3 expression via interacting with ALYREF, thereby facilitating NSCLC migration, invasion, and EMT.

An actinomycin D assay was conducted to analyze the effect of RBM15 silencing on XPR1 mRNA stability...RBM15-mediated m6A modification of XPR1 promoted the malignant progression of lung adenocarcinoma. These findings provide new insights into the molecular mechanism underlying the pathogenesis of LUAD and suggest potential therapeutic strategies for the treatment of this devastating disease.

NSUN3 aggravates SA-AKI by stabilising TIFA mRNA through m5C, indicating that NSUN3 may be a biomarker for SA-AKI.

The molecular mechanism of NAT10 function was analyzed using bioinformatics, ac4C- RNA immunoprecipitation, and actinomycin D treatment assay...Mechanistically, NAT10 stabilizes CAPRIN1 by promoting its ac4C modification. These findings suggest that NAT10 may be a promising therapy target for OC.

P3, N=280, Not yet recruiting, Gamaleya Research Institute of Epidemiology and Microbiology, Health Ministry of the Russian Federation

Mechanistically, OST-01 induces ferroptosis by downregulating LRP8-regulated selenoproteins, i.e., GPX4. A shift from a basal-mesenchymal to a luminal-epithelial state of breast cancer stem cells (BCSCs) as supported by the downregulation of stemness (e.g., CD44) and mesenchymal (e.g., FN1 and vimentin) markers, along with the upregulation of differentiation markers (e.g., CD24) and luminal-epithelial markers (e.g., CK19), was also observed.

This discovery highlights the significance of circWDR78 as a potential regulatory axis of miR-653-3p/RGS4 in CRC progression.

P1, N=175, Not yet recruiting, Johns Hopkins University

METTL1-amplified liposarcomas were hypersensitive to actinomycin D, a clinical inhibitor of ribosome biogenesis. We propose that METTL1 overexpression promotes sarcomagenesis by stimulating tRNA aminoacylation, protein synthesis, and tumor cell growth independent of its methyltransferase activity.

Consequently, these derivative compounds Cordycepin have the potential to be utilized as lead molecules in the development of highly effective and potent EGFR tyrosine kinase inhibitors for the treatment of breast cancer patients.

CDYL expression was detected after actinomycin D and RNase R treatment...hnRNPA2B1 mechanistically elevated the m6A level of circCDYL while decreasing its expression, which in turn reduced the binding of circCDYL to EIF4A3 and enhanced PHF8 expression. In summary, hnRNPA2B1-mediated m6A modification decreases circCDYL expression, which inhibits the interaction of circCDYL with EIF4A3, enhances PHF8 expression, and ultimately facilitates CRC progression.

CircCCT2 promotes HNSCC development through the miR-146a-5p/IRAK1 axis, revealing that circCCT2 is a potential biomarker and target for HNSCC.

P4, N=120, Recruiting, Johns Hopkins Bloomberg School of Public Health | Trial primary completion date: Jan 2025 --> Dec 2025

This study suggests that WTAP-mediated m6A modification of TRAIL-DR4 suppresses MH7A cell apoptosis. This discovery offers a new focus and avenue for the clinical treatment of RA, while also extending our understanding of the pathophysiology of RA from the standpoint of m6A alteration.

P1, N=40, Recruiting, Centre Hospitalier Universitaire de Saint Etienne | Trial completion date: Mar 2025 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Jun 2025

P2, N=0, Withdrawn, Children's National Research Institute | N=14 --> 0 | Trial completion date: Dec 2025 --> Dec 2024 | Recruiting --> Withdrawn | Trial primary completion date: Dec 2025 --> Dec 2024

P3, N=1134, Not yet recruiting, NICHD Global Network for Women's and Children's Health | Phase classification: P1 --> P3

Additionally, THP, a commonly used anthracycline chemotherapy drug, was found to downregulate circDUSP16, suggesting that its therapeutic effects on TNBC may be mediated through circDUSP16/miR-1224-3p/TFDP2 pathway. Our findings suggest that circDUSP16 is a promising biomarker and potential therapeutic target for TNBC.

In HCC, LIMA1 functions as a tumor promoter and engages with the WNT-β-catenin and Hippo signaling pathways,, affecting the characteristics of tumor cells. LIMA1 expression is regulated by METTL3-mediated m6A modification, leading to its high expression in HCC. Our research presents a hopeful objective for the detection and therapy of HCC.

P=N/A, N=20, Recruiting, Duke University | Trial completion date: Jun 2025 --> Jun 2026 | Trial primary completion date: Oct 2024 --> Oct 2025

P4, N=434, Terminated, Centre Hospitalier Universitaire de Saint Etienne | N=850 --> 434 | Recruiting --> Terminated; Lack of inclusons

This study indicated that cordycepin exerted antidepressant effect by modulating GSK3β/β-catenin pathway, suggesting its potential as a candidate agent for depression.

We revealed that the HIF1A inhibitors echinomycin (EC) and YC-1 upregulated CXCL10/11 genes induced by IFN-γ in tumor cells in vitro...Combination therapy enhanced tumor infiltration of CD8 T cells and suppressed tumor angiogenesis. The present study suggests that HIF1A signaling in tumor cells dominates ICI resistance via the downregulation of tumor-derived CXCL10/11.

The combination of TURBT with pirarubicin and BCG intravesical instillation significantly lowers the recurrence rate in HRNMIBC patients and enhances both quality of life and immune function recovery. Independent factors affecting HRNMIBC recurrence include tumor number, stage, grade, and primary tumor status.

In conclusion, HO has an inhibitory effect on NASH fibrosis. This effect is mediated by targeting upregulation of hepatocyte FXR, which in turn attenuates hepatocyte apoptosis and thus indirectly inhibits the activation of HSCs.

P1, N=1134, Not yet recruiting, NICHD Global Network for Women's and Children's Health

Overall, our investigation demonstrated that nigericin and dactinomycin play therapeutic roles in tumours by promoting RMS cell pyroptosis. Interference with GEFT and drug combination can exert a great inhibitory effect on tumours.

Results demonstrated that CMSSF has the potential to be used as a natural growth promoter to enhance immunity, antioxidation, as well as overall health and growth performance of grower pigs.