Upon PEGylation and Actinomycin D (ActD) loading, the resulting FessMOF/ActD-PEG nanoplatform induces marked DNA damage and lipid peroxidation. Concurrently, we found that ActD can inhibit Xc- system and elicit ferritinophagy, which further boosts the ferrotherapeutic efficacy of the FessMOF/ActD-PEG. In vivo experiments demonstrate that our fabricated nanoplatform presents excellent biocompatibility and a high tumor inhibition rate of 91.89%.

P4, N=50, Not yet recruiting, Boston Children's Hospital

P1, N=32, Completed, TenNor Therapeutics Inc.

However, despite the massive increase in the number of marine natural products classified as 'anticancer leads,' most of which correspond to general cytotoxic agents, and only a few have been characterized regarding their molecular targets and mechanisms of action. The current review presents a critical analysis of inhibitors of HIF-1 and HIF-2 and hypoxia-selective compounds that have been sourced from marine organisms and that might act as new chemotherapeutic candidates or serve as templates for the development of structurally similar derivatives with improved anticancer efficacy.

P4, N=100, Recruiting, Johns Hopkins Bloomberg School of Public Health | Not yet recruiting --> Recruiting

P=N/A, N=250, Recruiting, University of Minnesota

P1, N=40, Recruiting, Centre Hospitalier Universitaire de Saint Etienne

Subsequently, the stability of circRNA was evaluated through Ribonuclease R and actinomycin D treatment assays...Silencing circSNX6 also suppressed tumor formation and the metastasis of HCC cells in a mouse model. In summary, our findings suggest that circSNX6 promotes cell proliferation, metastasis, and angiogenesis in HCC by regulating the miR-383-5p/VEGFA pathway.

These results indicate that cordycepin potentiates the chemotherapeutic property of gemcitabine against CCA, which results from the downregulation of its cancer-stem-like properties. Hence, the combination therapy of cordycepin and gemcitabine may be a promising therapeutic strategy in the treatment of CCA.

Analogue 3 exhibited superior in vivo efficacy to echinomycin without significant toxicity in mouse xenograft model. The low dose of 3 needed to be efficacious in vivo is also noteworthy and our data suggest that 3 is an attractive and potentially novel agent for the treatment of colon cancer.

In this study, we investigated whether mEHT accelerates the tumor-specific delivery of doxorubicin (DOX) from lyso-thermosensitive liposomal doxorubicin (LTLD) and improves its anticancer efficacy in mice bearing a triple-negative breast cancer cell line (4T1)...The body weight loss was similar in all mice treated with any DOX formulation, suggesting no difference in toxicity. In conclusion, LTLD combined with mEHT represents a novel approach for DOX delivery into cancer tissue.

EZH2, miR-142-3p, lncRNA KCNQ1OT1, LIN28B, and HMGB3 expressions in glioma tissues and cells were determined using qRT-PCR or Western blot, followed by CCK-8 assay detection of cell viability, Transwell detection of invasion and migration, ChIP analysis of the enrichment of EZH2 and H3K27me3 on miR-142-3p promoter, dual-luciferase reporter assay and RIP validation of the binding of miR-142-3p-KCNQ1OT1 and KCNQ1OT1-LIN28B, and actinomycin D detection of KCNQ1OT1 and HMGB3 mRNA stability...EZH2 silencing depressed tumor growth and metastasis in nude mice via the miR-142-3p/KCNQ1OT1/HMGB3 axis. In conclusion, EZH2 curbed miR-142-3p expression, thereby relieving the inhibition of KCNQ1OT1 expression by miR-142-3p, enhancing the binding of KCNQ1OT1 to LIN28B, elevating HMGB3 expression, and ultimately accelerating glioma cell proliferation, invasion, and migration.

The stability of circSTRBP was assessed by actinomycin D and Ribonuclease R treatment...Additionally, exosomal circSTRBP promoted the tumour growth of GC cells in the xenograft model. Exosomal circSTRBP is implicated in the progression of GC by modulating the activity of miR-1294/miR-593-3p/E2F2 axis.

However, cell treatment with the ferroptosis inhibitor, ferrostatin‑1, or inducer, erastin, could not significantly reduce or promote, respectively, the expression of NOX2. However, GSK significantly affected ferroptosis and GPX4 expression. Overall, the results of the present study indicated that food therapy with Sc ameliorated CTP via inhibition of apoptosis and ferroptosis through regulation of NOX2‑induced oxidative stress, thus suggesting that Sc may be a potential therapeutic drug against CTP.

The relation between WTAP and lamin B1 (LMNB1) was verified by Methylated RNA Immunoprecipitation (meRIP) assay, RIP assay, dual-luciferase reporter assay and Actinomycin D assay...Additionally, WTAP affected the pathways of NF-κB and JAK2/STAT3 by LMNB1. WTAP-mediated m6A promoted the inflammation, mitochondrial damage and ferroptosis in LPS-induced HK-2 cells by regulating LMNB1 expression and activating NF-κB and JAK2/STAT3 pathways.

The impacts of HuR on CCL5 stability and activity of CCL5 promoter were evaluated using actinomycin D treatment and luciferase reporter assay...Rescue experiments showed that depletion of CCL5 in M2 macrophages reversed MEG3-induced suppressive effect on cell migration, invasion, and tube formation. MEG3 suppresses HCC progression by promoting M1-like while inhibiting M2-like macrophage polarization via binding to HuR and thus upregulating CCL5.

Me-RIP and Actinomycin D assays were performed to study ALKBH5's influence on CPT1A, the FAO rate-limiting enzyme...ALKBH5 mediates CPT1A upregulation by removing m6A modification, promoting M2 macrophage polarization and facilitating CRC development. These findings indicate that ALKBH5 enhances fatty acid metabolism and M2 polarization of macrophages by upregulating CPT1A, thereby promoting CRC development.

We found that treatment with cholesterol-lowering drugs such as lovastatin and simvastatin promoted cell apoptosis in all RMS lines by reducing Akt1 and Cav1 levels and increasing intracellular ROS levels...Furthermore, in combination with the chemotherapeutic agent actinomycin D, statins were effective in reducing cell survival through increased apoptosis. Taken together, our findings suggest that the molecularly linked signature formed by Akt1, Src, Cav1, and catalase may represent a prognostic determinant for identifying subgroups of RMS patients with higher probability of recurrence after radiotherapy. Furthermore, statin-induced oxidative stress could represent a treatment option to improve the success of radiotherapy.

Hsa_circ_0005397 promotes progression of hepatocellular carcinoma through EIF4A3. These research findings may provide novel clinical value for hepatocellular carcinoma.

m6A modification was evaluated using methylated RNA immunoprecipitation and dual-luciferase reporter assays, and E2F3 stability was assessed using Actinomycin D. The roles of FTO and E2F3 were also elucidated in vivo...Taken together, FTO silencing inhibited the malignant processes of RB by suppressing E2F3 in an m6A-YTHD2-dependent manner. These findings suggest that FTO is a novel therapeutic target for RB.

Our data indicated that circPDHK1-encoded PDHK1-241aa promotes ccRCC progression by interacting with PPP1CA to inhibit AKT dephosphorylation. This study provides novel insights into the multiplicity of circRNAs and highlights the potential use of circPDHK1 or PDHK1-241aa as a therapeutic target for ccRCC.

HNRNPL promotes S100A9 mRNA stability and expression through RBP action, thereby promoting ferroptosis in HCC cells.

It is demonstrated that circZCCHC2 plays a crucial role in the malignant progression of TNBC via the miR-1200/TPR axis, thereby activating the RAS-RAF-MEK-ERK pathway. The present results indicate that circZCCHC2 has the potential to serve as a novel prognostic biomarker for TNBC.

P4, N=100, Not yet recruiting, Johns Hopkins Bloomberg School of Public Health | Initiation date: Jan 2024 --> Apr 2024

The effects of HNRNPC and m6A regulators on WDR77 were investigated by actinomycin D assay...Notably, this regulation axis was closely tied to the m6A modification status of WDR77 mRNA. Overall, a critical regulatory mechanism was identified, as well as promising targets for potential treatment strategies for luminal breast cancer.

Exosomal A1BG-AS1 was m6A-modified by the m6A methyltransferase ZC3H13 to stabilize expression and thus prevent PCa cell malignancy. These findings offer a possible target for clinical therapy of PCa.

The resulting organoids were treated with pirarubicin or gemcitabine at 37 °C or 42 °C. Finally, RNA sequencing revealed the IFN-γ signaling pathway to be associated with hyperthermia. Overall, hyperthermia combined with chemotherapy exerted better therapeutic effects than those of normothermic chemotherapy in grade 1-2 non-muscle-invasive bladder cancer, potentially through activation of the IFN-γ-JAK-STAT pathway.

Mechanistically, RIP-seq and actinomycin D experiments results showed that IGF2BP2 enhanced the expression of Creatine Kinase B (CKB) by binding to CKB mRNA and enhancing its mRNA stability. Thus, IGF2BP2 inhibited ccRCC metastasis through enhancing the expression of CKB. Taken together, these finding suggests that IGF2BP2 is a novel metastasis suppressor of ccRCC and may serve as a potential therapeutic target.

Our in vitro findings may help to understand the role of zinc homeostasis in BCR-ABL regulation and thus highlight the importance of zinc homeostasis in CML.

P4, N=353323, Completed, Harvard Pilgrim Health Care | Active, not recruiting --> Completed

The stability of circXRN2 was confirmed through RNase R and actinomycin D experiments...Mechanistically, the dysregulated expression of circXRN2 had an impact on the expression of proteins within the EMT signaling pathway. Our results demonstrated that circXRN2 promoted the proliferation and metastasis of CRC cells through the miR-149-5p/ENC1/EMT axis, suggesting that circXRN2 might serve as a potential therapeutic target and novel biomarker in the progression of CRC.

We demonstrated that MEG3 is influenced by METTL3/YTHDF2 methylation and restrains ovarian cancer proliferation and metastasis by binding miR-885-5p to increase VASH1 expression. MEG3 is expected to become a therapeutic target for ovarian cancer.

The mitochondrial membrane potential decreased continuously and the positive expression rate decreased. It was speculated that compound 4a induced the apoptosis of MCF7 cells through the mitochondrial pathway.

RNA immunoprecipitation, actinomycin D treatment, and chromatin immunoprecipitation showed that MIR205HG may bind to human antigen R (HuR, ELAVL1) and stabilized JMJD2C expression, and JMJD2C may increase the enrichment of H3K9me3 in the ALKBH5 promotor region to promote ALKBH5 transcription. The tumor xenograft assay based on subcutaneous injection of sh-MIR205HG-treated melanoma cells showed that silencing MIR205HG suppressed tumor growth and reduced Ki67 positive rate by inactivating the JMJD2C/ALKBH5 axis. Generally, MIR205HG facilitated proliferation, invasion, and migration of melanoma cells through HuR-mediated stabilization of JMJD2C and increasing ALKBH5 transcription by erasing H3K9me3.

P3, N=808, Active, not recruiting, Children's Oncology Group | Trial completion date: Jan 2024 --> Jan 2025

UTP11 is potentially a diagnostic molecule and a therapeutic candidate for treatment of HCC.

RIP, RNA pull-down, and actinomycin D assays were performed to determine the associations between NEAT1, UPF1, and Apelin...Moreover, NEAT1 knockdown reduced HG- and IH-induced injury to HMEC-1 cells through Apelin. NEAT1 silencing reduced HMEC-1 cell injury through the Apelin/Nrf2/HO-1 signalling pathway in T2DM-OSA.Abbreviations: LncRNAs, long non-coding RNAs; T2DM, type 2 diabetes mellitus; OSA, obstructive sleep apnoea; NEAT1, nuclear paraspeckle assembly transcript 1; IH, intermittent hypoxia; HMEC-1, human microvascular endothelial cells; HG, high glucose; Nrf2, NF-E2-related factor 2; UPF1, up-frameshift suppressor 1; HO-1, haem oxygenase-1; qRT-PCR, quantitative real-time polymerase chain reaction; ELISA, enzyme-linked immunosorbent assay; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; TNF-α, tumour necrosis factor-α; CCK-8, Cell Counting Kit-8; IL-1β, interleukin-1β; ROS, reactive oxygen species; MDA, malondialdehyde; SOD, superoxide dismutase; RIP, RNA immunoprecipitation; SD, standard deviations; GSH, glutathione; AIS, acute ischaemic stroke; HMGB1, high mobility group box-1 protein; TLR4, toll-like receptor 4.

P4, N=100, Not yet recruiting, Johns Hopkins Bloomberg School of Public Health

No abstract available

P3, N=808, Active, not recruiting, Children's Oncology Group | Trial completion date: Dec 2024 --> Jan 2024

FT895, an HDAC11 inhibitor, exhibits potent anti-tumor effects on MPNST cells and enhances the cytotoxicity of cordycepin against MPNST...The RNA-seq analysis underscored the prominent role of the HIF-1α signaling pathway post-FT895 treatment, aligning with the observed impairment in mitochondrial respiration. In summary, the study pioneers the revelation that FT895 induces mitochondrial respiratory damage in MPNST cells.

Validated by qRT-PCR, PCR, sanger sequencing, actinomycin D and RNase R digestion experiments, hsa_circ_0001583 was proved to be a genuine circular RNA with higher expression levels in bladder cancer tissue...In summary, our study is the first to highlight the upregulation of hsa_circ_0001583 in bladder cancer and its role in downregulating miR-126-3p by binding to and stabilizing the SND1 protein, thereby promoting bladder cancer cell migration and invasion. This study adds hsa_circ_0001583 to the pool of bladder cancer metastasis biomarkers and therapeutic targets.