MYC expression

P3, N=302, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: May 2024 --> May 2025 | Trial primary completion date: May 2024 --> May 2025

ZNF471 binding to c-Myc gene promoter suppressed oncogene c-Myc expression, thereby playing the anti-cancer effect and enhancing TSCC sensitivity to docetaxel. In all, N-glycosylation of ZNF471 affects the proliferation, invasion, and docetaxel sensitivity of TSCC via regulation of c-Myc.

Further studies revealed that 21r inhibited proliferation by decreasing the expression of proto-oncogene c-Myc, blocking cell cycle in G0/G1 phase, and inducing apoptosis in MV-4-11 cells in a dose-dependent manner. All the results showed that compound 21r was a potent BRD4 inhibitor with BD1 selectivity, which had potential in treatment of leukemia.

Single-cell RNA sequencing of human clinical HGSC samples revealed a strong negative association between cancer cell-intrinsic MYCN transcriptional program and type I IFN signaling. Thus, N-MYC inhibits tumor cell-intrinsic innate immune signaling in HGSC, making it a compelling target for immunotherapy of cold tumors.

With the limitation of the low number of patients analysed, this study suggests that differences in immunetranscriptomic profile are associated with response to Aza-Ven in newly diagnosed unfit-for-chemotherapyAML patients. Some specific gene expression patterns are differentially shown at diagnosis in responders ascompared to refractory patients, while interesting and still unexplored pathways and signals, such as T-cellsactivation and priming, and antigen presentation, were described in responder patients during therapy andrelated to incoming relapse. Further studies on larger cohorts of patients are highly warranted to confirm ourpreliminary findings.

Notably, singular TP53 mutations inadequately explain pathway dysregulation, emphasizing the need to explore additional contributing factors. These findings illuminate the intricate interplay among TP53 mutations, HOPS/TMUB1, and apoptotic pathways, providing valuable insights for targeted cancer interventions.

Amplified MYCN does not confer resistance to opaganib, and, in fact, the drug attenuates the expression of both c-Myc and N-Myc. The safety of opaganib has been established in clinical trials with adults with advanced cancer or severe COVID-19, and so opaganib has excellent potential for treating patients with NB, particularly in combination with temozolomide and irinotecan or anti-CTLA-4 antibody.

Our results suggest that the LATS2-YAP1-BIRC3/5 axis participates in the RE cell proliferation and promotes rumen growth during the preweaning period.

It could transcriptionally inhibit the expression of c-Myc, induce cell cycle arrest in the G0/G1 phase and apoptosis in MV4-11 cells. This study thus provided us a new chemotype for the development of drug-like PROTACs targeting p300/CBP, which is expected to be applied in cancer therapy.

Finally, CD44 targeting can be a good treatment option to make BC cells more sensitive to apoptosis.

Our study supports the concept that MYC represents an Achille's heel in MM across disease states and that MYCi975 may be a promising therapeutic for patients with MM, particularly in combination with IMiDs.

Importantly, the WNK inhibitor WNK463 inhibits MM growth in primary patient samples as well as xenograft mouse models and exhibits synergistic effects with various anti-MM compounds. Collectively, our study uncovers WNK1 as a potential therapeutic target in MM.

This study revealed that FOXO3 polymorphisms influence the RMS susceptibility and prognosis in children, and might altered the expression of FOXO3. FOXO3 polymorphism was suggested as a biomarker for RMS susceptibility and prognosis.

In addition, SNHG15 inhibited ferroptosis through an HNRNPA1-dependent regulation of SLC7A11/GPX4 axis. Our results support a novel model in which E2F1- and MYC-activated SNHG15 regulates ferroptosis via an HNRNPA1-dependent modulation of the SLC7A11/GPX4 axis, which serves as the critical effectors in GC progression, and provides a new therapeutic direction in the treatment of GC.

Notably, the MYC-S100A9 circuit provokes a complex network of inflammatory signaling that involves numerous hematopoietic cell types in the bone marrow microenvironment. Accordingly, genetic ablation of S100A9 or treatment with small molecules targeting the MYC-S100A9 pathway effectively ameliorates MF phenotypes, highlighting the MYC-alarmin axis as a novel therapeutic vulnerability for this subgroup of MPNs.

Dietary acetate supplementation promotes tumour growth and inhibits CD8+ T cell infiltration, whereas disruption of acetate uptake inhibits immune evasion, which increases the efficacy of anti-PD-1-based therapy. These findings highlight a critical role of acetate promoting tumour growth beyond its metabolic role as a carbon source by reprogramming tumour metabolism and immune evasion, and underscore the potential of controlling acetate metabolism to curb tumour growth and improve the response to immune checkpoint blockade therapy.

The higher the expression of MYC and NCAPG2, the worse the prognosis. MYC and NCAPG2 are core molecules in gastric cancer.

Furthermore, the incubation of zebrafish embryos with breast tumor homogenates induced the expression of c-Myc and HER-2 as tumor markers, contrasting to embryos exposed to healthy tissue-derived material. This study confirms and extends our hypothesis that tumor homogenates contain and may act as vectors for "malignancy drivers," which ultimately implement a carcinogenesis process in otherwise healthy mice.

KLHDC3 mRNA abundance was associated with prognosis in pancreatic cancer patients with a low level of SHISA2 gene expression. These results suggest that KLHDC3 cooperates with Fbxw7 to promote c-Myc degradation in a subset of cancer cells with low GSK3 activity.

Our study provides a better understanding of the interaction between GBM cells and gestational tissue-derived hMSCs. This knowledge might be used to develop safer and more effective stem cell therapy that improves the survival and quality of life of patients with GBM by manipulating the interaction between hMSCs and GBM cells.

Our data provide a novel insight into the potential interactions of MYC and PVT1 with other genes. Moreover, we identified a new PARP inhibition mechanism down-regulating MYC, as well as the linear and circular PVT1 transcripts. Future work should expand on clinical studies to better understand the prognostic role of PVT1 in OC.

Furthermore, Isoimperatorin suppressed the overexpression of c-Myc by the proteasome inhibitor MG132 and also disturbed cycloheximide-treated c-Myc stability in Huh7 cells. Overall, these findings support the novel evidence that the pivotal role of c-Myc and SIRT1 is critically involved in Isoimperatorin-induced apoptosis in HCCs as potent molecular targets in liver cancer therapy.

A mechanistic investigation demonstrated that exposing lung cancer cells to CLs downregulated the phosphorylation of Akt and mTOR, as well as c-Myc expression. Based on these findings, we believe that CLs may have beneficial effects on health as they potentially suppress EMT and CSCs, as well as the cancer-potentiating pathway of Akt/mTOR/c-Myc.

In conclusion, CKE prevents the growth of tumors on mouse skin by reducing oxidative stress and suppressing c-MYC overexpression brought on by DMBA/TPA induction. This makes it an effective dietary antioxidant with anti-tumor properties.

Together, these data suggest that the IL-33/ST2 pathway may be involved in the crosstalk between the tumour and immune cells by modulating the phenotype of head and neck SCC and T cell activity. IL-33 neutralisation may offer a novel therapeutic strategy for SCC.

We propose that it is possible to induce similar effects in patients using CDK9 inhibition, which, we show, causes DNA damage in vitro. In the future, it is important to establish whether CDK9 inhibitors can potentiate the effects of immunotherapy against late-stage prostate cancer, a currently lethal disease.

A similar effect was observed in non-transformed human RPE-1 cells compared to a tumor cell line (HeLa) that overexpresses MYC . These results demonstrate that TPX2 alters spindle length and morphology in cancer cells, which may contribute their ability to divide despite MYC-induced mitotic stress.

This study explored the hub genes and related mechanisms of RA and NSCLC, demonstrated the central role of the inflammatory response and the adaptive immune system, and identified PTPRC as an immune-related biomarker and potential therapeutic target for RA and NSCLC patients. In addition, PTPRC can significantly promote the proliferation, migration and invasion of A549 cells, and its mechanism may be to promote the EMT process by regulating the Wnt signaling pathway and promote cell stemness, which in turn has a promoting effect on A549 cells.

Interfering with c-Myc in established tumors using the Bromodomain and Extra-Terminal motif inhibitor JQ-1 diminished liver tumor growth in c-Jun~Fra-2 mutant mice. Thus, our data establish c-Jun~Fra-2hep mice as a model to study liver tumorigenesis and identify the c-Jun/Fra-2-Myc interaction as a potential target to improve HCC patient stratification and/or therapy.

Notably, hormonal administration of diethylstilbestrol (DES) or progesterone (P4) upregulated oviduct-specific genes in these cells...The established immortalized cOECs overcome previous challenges associated with long-term culture and maintenance, providing a reliable platform for efficient protein production validation. This study presents a comprehensive characterization of the immortalized cOECs, addressing critical limitations associated with in vivo systems and laying a foundation for the development of a streamlined and effective chicken bioreactor model.

MNDA was highly expressed in MZL with a potential utility in differential diagnosis between MZL and RLH as well as FL, whereas its value in distinguishing MZL from MCL, CLL/SLL is limited. In addition, MNDA expression in DLBCL was more frequently seen in the non-GCB group and the BCL2/MYC double-expression group, and demonstrated a correlation with CD5, which deserves further investigation. The clinical relevance of MNDA and its correlation with the prognosis of these lymphomas also warrant to be fully elucidated.

This indicated that the miR-150 binding site region is dispensable for the growth promoting role of circZDHHC11. To conclude, our results show that circZDHHC11 is a crucial factor supporting BL cell growth independent of its ability to sponge miR-150.

We discovered that STK16 phosphorylates c-MYC at serine 452, hindering its degradation via the ubiquitin-proteasome pathway. STK16 inhibition, either genetically or pharmacologically, effectively curtails cancer growth and c-MYC expression in vivo. These findings highlight STK16 as a potential therapeutic target for colorectal cancer.

In addition, we found that quercetin downregulates c-Myc expression in two BC cell lines. This study revealed the effective ingredients and latent molecular mechanism of action of CSSGF against TNBC and confirmed that quercetin could target c-Myc to induce anti-BC effects.

The clinical translation of this method necessitates further investigation and validation. In summary, the Ro-3306-loaded magnetic-driven hydrogel micro-robots present a novel strategy for enhancing the chemosensitivity of MYC-dependent osteosarcoma, paving the way for new possibilities in future clinical applications.

High MYC and NCAPG2 expression has been observed in colorectal cancer, and increased MYC and NCAPG2 expression correlates with worse prognosis.

Its antitumor activity is illustrated in an orthotopic mouse xenograft mammary tumor model. Overall, our results show that SDU-071 is a viable option for potentially treating TNBC as a new BRD4-p53 inhibitor.

Through mouse xenograft assays, we demonstrate that the phospho-deficient PKM2-S333A mutant promotes tumor growth in vivo. In conclusion, we identified a ULK1-PKM2-c-Myc axis in inhibiting breast cancer, and a glucose-sensitive phosphorylation of PKM2 in modulating the Warburg effect.

Decreases of αSMA deposition in the CD248 knockout KPC mice remodel the tissue stroma and downregulated TOP2A expression in the epithelium. In summary, stromal stiffness induces the onset of cells-of-origin of cancer by ectopic TOP2A expression, and the genomic amplification of MYC-PTK2 locus via alternative transdifferentiation of pancreatic progenitor cells is the vulnerability useful for disintegrin KG treatment against cells-of-origin cancer.

This study contributes to understanding the mechanisms of Imatinib resistance in CML, proposing IL6R and MYC as pivotal targets for therapeutic strategies. Moreover, the utilization of NIADS v2 enhances our capability to analyze apoptosis and drug responses, contributing to a deeper understanding of CML pathogenesis and treatment options.

Finally, LY2090314 caused gene expression dysregulation mainly involving pathways related to transcription regulation, cell proliferation, and chromatin remodeling. For the first time, our work provides the underlying molecular basis for synthetic lethality due to cohesin mutations and suggests that targeting the WNT may be a promising therapeutic approach for tumors carrying mutated cohesin.

Overall, we identify a small group of genes highly enriched within functional gene categories related to mitotic processes that are commonly regulated by N-MYC, WDR5, and PDPK1 and suggest that a tripartite interaction between the three regulators may be responsible for setting the level of mitotic gene regulation in N-MYC amplified cell lines. This study provides a foundation for future studies to determine the exact mechanism by which N-MYC, WDR5, and PDPK1 converge on cell cycle related processes.