dactinomycin

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.

P3, N=110, Not yet recruiting, Children's Oncology Group

RIP, dual luciferase reporter gene and actinomycin D assay were conducted to verify the interactions between RBM15 and its targeted gene, and the presence of m6A modification site of its targeted mRNA, respectively...RBM15 regulated E2F2 in an m6A modification-dependent manner thereby boosting malignant cellular processes in CRC. The RBM15/E2F2 axis may be a novel target for CRC therapy.

m6A-modified circXPO1 by ALKBH5/IGF2BP2 axis destabilized WWC2 via interaction with FMRP to activate Hippo-YAP pathway, thereby facilitating CRC growth and metastasis. Targeting circXPO1 might be a potential therapeutic strategy for CRC.

The stability of PCNA mRNA was assessed after treatment with actinomycin D. An in vivo nude mouse xenograft model was created to validate the role of RBM15B...Furthermore, PCNA overexpression mitigated the effects of RBM15B knockdown on PC cell proliferation. In conclusion, RBM15B promotes PC cell proliferation by enhancing the stability of PCNA mRNA through YTHDF1-mediated m6A modification.

KDM4A silences BMP9 expression by removing histone methyl groups from the BMP9 gene region, leading to further enhancement of glutamine metabolism, which contributes to malignant tumor progression. In addition, using JIB-04 in combination with exogenous BMP9 could inhibit the malignant progression of breast cancer cells and the growth of tumors more significantly.

CDK1 mRNA stability was detected through actinomycin D assay...Furthermore, HAND2-AS1 impeded HB cell proliferation and cycle progression while inducing cell apoptosis by downregulating CDK1. Our research highlights that HAND2-AS1 can exert a tumor-suppressive effect on HB through the negative regulation of CDK1, and the HAND2-AS1/CDK1 is expected to be a diagnostic molecular marker and therapeutic target for HB in clinical practice.

A total of 41 drugs, including dactinomycin, luminespib, and sepantronium bromide, had a significant difference in IC50 between the 2 subgroups. We demonstrated the potential of a novel signature constructed from 4 P. gingivalis-related IRRGs for prognostic prediction in ESCC patients.

Actinomycin D was used to evaluate mRNA stability...Furthermore, Lico A could affect the MDM2/p53 pathway by downregulating IGF2BP3 expression. Lico A exerts the anti-proliferative and pro-ferroptosis activity in AML cells by affecting the IGF2BP3/MDM2/p53 pathway, providing new evidence for Lico A as a promising agent for the treatment of AML.

The properties of circRNA were verified by RNase R, actinomycin D, and fluorescence in situ hybridization (FISH)...Knockdown of its expression inhibits cell proliferation, invasion, EMT and autophagy and promotes apoptosis. CircBIRC6/miRNA-574-5p/DNAJB1 is a molecular axis that regulates prostate cancer cells.

Our findings showed that AZD1775 promoted ferroptosis by blocking cystine uptake, an action similar to that of Erastin...Remarkably, we found that the nucleolar stress-inducing agent Actinomycin D (Act...Altogether, our study demonstrates that AZD1775 promotes ferroptosis by targeting cystine uptake but also mediates the adaptive activation of SLC7A11 through the WEE1-SETDB1 cascade and NRF2-induced transcription, and inhibition of SLC7A11 by Act. D boosts the anti-tumor efficacy of AZD1775 by enhancing ferroptosis in cancers with wild-type p53.

Additionally, actinomycin D, methylated RNA immunoprecipitation, and qRT-PCR assays were performed to examine the regulatory effects of ZC3H13 on the DLX6-AS1 m6A modification. In conclusion, ZC3H13 knockdown enhances the inhibitory effect of sevoflurane on GC cell malignancy by inducing DLX6-AS1 m6A modification. Our findings may help identify potential therapeutic targets for the treatment of GC.

METTL14/IGF2BP2-mediated m6A modification of STEAP1 aggravated ALI induced by sepsis. These findings suggest potential therapeutic targets for the treatment of this disease.

P3, N=205, Recruiting, Children's Oncology Group | Trial completion date: Dec 2030 --> Jun 2030 | Trial primary completion date: Dec 2030 --> Jun 2030

CircRNA ATF6 suppresses BCa cell growth, migration and invasion through the miR-146a-5p/FLNA axis.

P=N/A, N=156, Active, not recruiting, Children's Hospitals and Clinics of Minnesota | Trial completion date: Dec 2024 --> Dec 2028 | Trial primary completion date: Dec 2022 --> Dec 2025

METTL3 and IGF2BP1-mediated m6A modification of ZHX2 promoted RCC progression. The finding suggests that ZHX2 may serve as a potential therapeutic target in RCC, providing valuable insights for future clinical interventions.

The stability of circ_0023179 was verified using ribonuclease R enzyme, actinomycin D and agarose gel electrophoresis...The downregulation of miR-615-5p and the upregulation of CDH3 mitigated the inhibitory effect of silencing circ_0023179 on NSCLC cell proliferation. In conclusion, silencing circ_0023179 inhibited NSCLC cell proliferation by targeting the miR-615-5p/CDH3 axis involved in NSCLC progression.

Messenger RNA stability was evaluated by qRT-PCR after treatment with actinomycin D. The methylated RNA immunoprecipitation (MeRIP) qPCR, dual-luciferase reporter analyses and m6A dot blotting were carried out to measure the m6A modification...Mechanistically, the downregulation of ASNS by STM2457 may be due to the decrease of m6A modification level in ASNS mRNA mediated by METTL3. Our findings suggest that STM2457 may serve as a potential therapeutic agent and ASNS may be a new promising therapeutic target for CRC.

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

RNase and actinomycin D were used to examine the features of circZEB1...Our study indicate that circZEB1 had oncogenic function in BC by focusing on circZEB1/miR-337-3p/OGT and YBX1. It might be inferred that circZEB1 could be a promising new target for BC treatment.

The half-maximal inhibitory concentration for doxorubicin, vincristine, and actinomycin-D was determined using CCK-8 assays. Overall, the findings of the present study demonstrate that UNC13B regulates the sensitivity of the Wilms' tumor 17.94 cell line to doxorubicin by modulating lysosome formation within cells. The results suggest that UNC13B is likely an enriched target involved in lysosomal regulation in certain tumors, offering a new approach for optimizing chemotherapy in Wilms' tumor and other cancers with high UNC13B expression.

METTL3 bound to IGF2BP1 and enhanced IGF2BP1's m6A recognition of TRPV1 mRNA, thereby promoting NSCLC cell growth and metastasis, and inhibiting M2 macrophage polarization.

Our results demonstrated that circRHBDD1 promoted GC immune escape by upregulating the expression of PD-L1 and reprogramming T cell-mediated immune response. Inhibition of circRHBDD1 expression could potentially enhance the response of GC patients to immunotherapy, thus improving treatment outcomes. Additionally, the development of a nanodrug delivery system provides a feasible approach for future clinical applications.

H. pylori-induced underexpression of METTL14 promotes the translation of HIF-1α and accelerates tumor progression by activating the PI3K/AKT pathway. These results provide novel insights into the carcinogenesis of GC.

Interestingly, other combinations of drugs, e.g., etoposide + nutlin-3a, actinomycin D + RG7112, and actinomycin D + idasanutlin had a similar effect. Moreover, normal human fibroblasts are less sensitive to death induced by ActD + Nut3a + FASLG. Our findings create the opportunity to revive the abandoned attempts of cancer immunotherapy employing the recombinant FAS ligand.

We demonstrated for the first time that mRNA expressed from this promoter actually produces the protein, which can be detected with Western blotting, in all examined cancer cell lines with wild-type p53 exposed to A + N. In some cell lines, it is also induced by clinically relevant camptothecin, by nutlin-3a acting alone, or by a combination of actinomycin D and other antagonists of p53-MDM2 interaction-idasanutlin or RG7112. This isoform, fused with green fluorescent protein, localizes in the perinuclear region of cells.

KDM5B mRNA stability was measured after actinomycin D treatment. In conclusion, RBM15 promoted KDM5B expression, and KDM5B upregulation inhibited ferroptosis and promoted DDP resistance in LC by downregulating FER1L4 and upregulating GPX4, as well as by upregulating KCNQ1OT1 and inhibiting ACSL4. Silencing RBM15 inhibited tumor growth in vivo.

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

Circ_0007386, regulated by YAP1-EIF4A3 interaction under hypoxia conditions, plays an oncogenic role in NSCLC progression via the miR-383-5p/CIRBP axis.

RNA stability assay was performed using actinomycin D. Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter experiments were performed to confirm the interaction between TFAP2A and cystine/glutamate antiporter solute carrier family 7 member 11 (SLC7A11) or glutathione peroxidase 4 (GPX4)...IGF2BP3 or TFAP2A knockdown induced ferroptosis by aggravating erastin-induced cell viability suppression, increasing the production of intracellular ROS, lipid ROS, and MDA, and decreasing GSH synthesis, GSH/GSSG ratio, and cystine uptake...IGF2BP3 suppresses ferroptosis in LUAD by m6A-dependent regulation of TFAP2A to promote the transcription of SLC7A11 and GPX4. Our findings suggest that targeting IGF2BP3/TFAP2A/SLC7A11/GPX4 axis might be a potential therapeutic choice to increase ferroptosis sensitivity in LUAD.

The identified METTL14-ANKRD22-SLC25A1 axis emerges as a promising therapeutic target for NPC, and also these molecules may serve as novel diagnostic biomarkers.

PI3K gene transcription was inhibited by co-culturing cells with actinomycin D, and the half-life of PI3K mRNA was calculated by measuring residual PI3K mRNA expression over different co-culture time...The fibrosis area was smaller in the Ang Ⅱ+sh-Mettl3 group than that in the Ang Ⅱ group (P<0.05), but increased again upon addition of SC79. Mettl3-mediated RNA m6A epigenetic regulation is involved in Ang Ⅱ-induced pericyte-to-myofibroblast transdifferentiation and renal fibrosis, potentially by affecting PI3K stability and regulating the PI3K/AKT signaling pathway.

Overexpression of NOP58 facilitates proliferation, migration, invasion, and stemness of NSCLC cells by stabilizing hsa_circ_0001550, hinting that NOP58 is a novel molecular target for NSCLC therapy.

These results indicate that by inhibiting the N-glycosylation of Wnt3, the proliferation, migration, invasion and colony formation abilities of liver cancer cells can be weakened, which might provide new therapeutic strategies for clinical liver cancer in the future.

To study the properties of circATIC, sanger sequencing, agarose gel electrophoresis and treatment with RNase R/Actinomycin D were utilized. Finally, circATIC promotes RCC2 expression to enhance Epithelial-Mesenchymal Transition (EMT) progression and activate JNK signal pathway, thus strengthening DDP resistance in BLca cells. Our study demonstrated that circATIC promoted BLca progression and DDP resistance, and could serve as a potential target for BLca treatment.

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