dactinomycin

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.

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.

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.

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

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.

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.

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.

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.

In human RD and RH30 lines, treatment with 0.01-1 μM doses of fatostatin (SREBP2 inhibitor), lovastatin and simvastatin (HMGCR inhibitors), and zoledronic acid (FDPS inhibitor) impaired cell growth and migration, which were conversely stimulated by 50-100 μM cholesterol (CHO) supplementation. Treatment of RMS lines with higher doses of SREBP2 and MVP inhibitors (5-50 μM) promoted oxidative cell death and chemosensitization in combination with actinomycin D. Administration of lovastatin or fatostatin to RD and RH30 cells produced a rapid attenuation of Erk1/2 and Akt1 phosphorylation, detectable after 4 hours of treatment...Taken together, these data suggest that the axis formed by Akt1, SREBP2 and MVP is critical for RMS tumor growth, migration, and oxidative stress protection mainly through the maintenance of CHO levels that ensure proper intracellular signaling. Therefore, targeting CHO levels by SREBP2 and MVP inhibition may represent a viable option to improve the combination therapy protocol in RMS.

P3, N=1656, Not yet recruiting, Children's Oncology Group | Initiation date: Dec 2024 --> Mar 2025

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.

Patients with fusion-positive N1 ARMS carry a poor prognosis. Adequate local treatment of LN improved survival.

P3, N=110, Not yet recruiting, Children's Oncology Group | Initiation date: Dec 2024 --> Mar 2025

P3, N=325, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Oct 2024 --> Oct 2025

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.

P2, N=28, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Dec 2027 --> Aug 2027 | Trial primary completion date: Dec 2026 --> Aug 2026

Our findings demonstrate SNHG14 plays a significant role in promoting chemoresistance of NPC cells to cisplatin through U2AF2/Notch2 axis. These results highlight potential therapeutic targets for NPC treatment.

Actinomycin D assay was performed to investigate the effect of PCBP2 depletion on TROAP mRNA stabilization...Our study demonstrated that PCBP2 stabilized TROAP to promote the malignant progression of gastric cancer. Targeting PCBP2 and its downstream target TROAP may provide a novel therapeutic strategy for the treatment of gastric cancer.

Our research suggests Hsa_circ_0072732 enhanced renal cell carcinoma sunitinib resistance by inhibiting ferroptosis through miR-548b-3p/SLC7A11.

The patient underwent a multimodal treatment approach, including bladder-preserving surgery, 12 cycles of high-dose MRTK-2020 neoadjuvant chemotherapy [comprising actinomycin D, vincristine, doxorubicin, cyclophosphamide (AVDC), ifosfamide, carboplatin, and etoposide (ICE)], followed by adjuvant radiotherapy. Despite the limited evidence base, bladder-preserving surgeries, when feasible, should be considered and accompanied by adjuvant therapies for optimal outcomes. This case illustrates the potential for successful treatment of pure MRTs of the bladder using a combination of surgery, chemotherapy, and radiotherapy.

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.

TRAF6 mRNA stability was tested using actinomycin D treatment...Meanwhile, ELAVL1 knockdown relieved caerulein-induced AR42J cell injury and macrophage M1 polarization, while these effects were abolished by TRAF6 overexpression. TRAF6, stabilized by ELAVL1, promoted caerulein-induced AR42J cell injury and macrophage M1 polarization, suggesting that it might accelerate AP9 progression.

P3, N=118, Recruiting, Children's Oncology Group | Active, not recruiting --> Recruiting

Actinomycin D treatment and RT‒qPCR assays were performed to determine the mRNA stability of AXIN1...Our study provides a new method for the treatment of asthma. This work not only deepens our understanding of the molecular underpinnings of asthma but also identifies potential therapeutic targets for the development of novel treatments aimed at inhibiting ASMC proliferation and alleviating asthma symptoms.

Furthermore, the interaction between MOV10 and integrin α3 (ITGA3) was verified by RNA immunoprecipitation assay, and the actinomycin D assay was used to detect ITGA3 mRNA stability...Furthermore, it was demonstrated that S100A16 regulated the stability of ITGA3 mRNA via MOV10 to mediate ECM‑receptor interactions. In conclusion, S100A16 may bind to MOV10 to stabilize ITGA3 mRNA and regulate ECM‑receptor interactions, hence contributing to the malignant progression of LUAD.

USP1 mRNA stability was determined after actinomycin D treatment...HOXA10 downregulation inhibited in vivo NPC proliferation through the PTPRG-AS1/USP1 axis. In conclusion, HOXA10 facilitates NPC cell proliferation in vitro and in vivo through the PTPRG-AS1/USP1 axis.

Taken together, our results confirm that HHT is a substrate for MDR1. It opens the door to a new opportunity to clinically evaluate HHT and its derivatives for the treatment of AML and other cancers.

The mRNA stability was analyzed using actinomycin D (ActD)... Our findings indicated that LINC01134 functioned as an oncogene in CRC by binding directly to SLC1A5 mRNA and increasing its stability. Therefore, targeting LINC01134 could be a potential therapeutic target for treating CRC.