The Molecular ‘Myc-anisms’ behind Myc-Driven Tumorigenesis and the Relevant Myc-Directed Therapeutics

McAnulty, Jessica; DiFeo, Analisa

doi:10.3390/ijms21249486

Cited by 15 publications

(11 citation statements)

References 223 publications

(200 reference statements)

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“…All MYC proteins mainly act as transcription regulators, regulating the expression of genes involved in a variety of cellular processes, proliferation, survival, metabolism, invasion, and metastasis ( Duffy and Crown, 2021 ). According to previous reports, among 33 different cancers, MYC amplification was found in 21% of patients, especially BRCA, UCEC, and OV ( McAnulty and DiFeo, 2020 ). High MYC has been reported to be associated with a poor prognosis of prostate cancer and breast cancer ( Maroto et al, 2017 ).…”

Section: Discussionmentioning

confidence: 84%

Differential Expression of the TLR4 Gene in Pan-Cancer and Its Related Mechanism

Feng

et al. 2021

Front. Cell Dev. Biol.

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Previous studies have revealed the relationship between toll-like receptor 4 (TLR4) polymorphisms and cancer susceptibility. However, the relationship between TLR4 and prognosis and immune cell infiltration in pan-cancer patients is still unclear. Through the Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) databases, the distinct expression of the TLR4 gene in 24 tumors and normal tissues was analyzed. Univariate Cox proportional hazards regression analysis was used to identify the cancer types whose TLR4 gene expression was related to prognosis. The relationship between TLR4 and tumor cell immune invasion was studied. Spearman’s rank correlation coefficient was used to analyze the relationship among TLR4 and immune neoantigens, tumor mutation burden (TMB), microsatellite instability (MSI), DNA repair genes, and DNA methylation. Gene Set Enrichment Analysis (GSEA) was used to identify the tumor-related pathways that the TLR4 gene was highly expressed in; the expression of the TLR4 gene was verified with the Human Protein Atlas (HPA) database. Low expression of TLR4 was associated with an inferior prognosis in kidney renal clear cell carcinoma (KIRC), skin cutaneous melanoma (SKCM), and uterine corpus endometrial carcinoma (UCEC), while high expression was related to a poor prognosis in head and neck squamous cell carcinoma (HNSC), prostate adenocarcinoma (PRAD), stomach adenocarcinoma (STAD), and testicular germ cell tumor (TGCT). The expression of TLR4 was negatively correlated with the expression of B cells in STAD. The expression of TLR4 was positively correlated with the infiltration of B cells, CD4 and CD8 T cells, neutrophils, macrophages, and dendritic cells in STAD, KIRC, UCEC, TGCT, and SKCM. The expression of the TLR4 gene in KIRC, SKCM, STAD, TGCT, and UCEC was highly correlated with inducible T-cell costimulator (ICOS), cytotoxic T lymphocyte-associated molecule 4 (CTLA4), and CD28 immune checkpoints. Spearman’s rank correlation coefficient showed that the expression of TLR4 gene was significantly correlated with TMB in STAD and UCEC and was prominently correlated with MSI in TGCT, STAD, and SKCM. The expression of the TLR4 gene was highly correlated with MLH1, MSH2, and MSH6 in KIRC, SKCM, and STAD. The expression of the TLR4 gene was remarkably correlated with the methyltransferases DNA methyltransferase 2 (DNMT2) and DNA methyltransferase 3-beta (DNMT3B) in SKCM and STAD. Enrichment analysis showed that TLR4 was highly expressed in the chemokine signaling pathway and the cell adhesion molecule and cytokine receptor interaction pathway. In summary, the expression of TLR4 is linked to the prognosis of KIRC, SKCM, STAD, TGCT, and UCEC patients and the level of immune infiltration of CD4, CD8 T cells, macrophages, neutrophils, and dendritic cells.

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Section: Discussionmentioning

confidence: 84%

Differential Expression of the TLR4 Gene in Pan-Cancer and Its Related Mechanism

Feng

et al. 2021

Front. Cell Dev. Biol.

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“…c-Myc serves as a master regulator of cellular metabolism and proliferation. Aberrant c-Myc activation stimulates numerous metabolic changes that not only promote oncogenic transformation but also support the malignant phenotypes of cancer cells [ 11 , 47 , 48 ]. The intracellular level of c-Myc is mainly regulated by its stability via the phosphorylation of its S62 and T58 sites ( Fig.…”

Section: Resultsmentioning

confidence: 99%

p53/FBXL20 axis negatively regulates the protein stability of PR55α, a regulatory subunit of PP2A Ser/Thr phosphatase

et al. 2021

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“…Direct c-Myc protein targeting does not seem to be an effective therapeutic approach. Conversely, targeting Myc transcription, disrupting Myc/Max dimerization, causing an interference in Myc protein stability, inhibiting Myc-associated cell cycle, and targeting metabolism through Myc target genes and cofactors are current anti-Myc strategies in cancer treatment (McAnulty and DiFeo, 2020).…”

Section: Discussionmentioning

confidence: 99%

Chemoresponse of de novo Acute Myeloid Leukemia to “7+3” Induction can Be Predicted by c-Myc-facilitated Cytogenetics

Hsiao

Wang

et al. 2021

Front. Pharmacol.

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Background: Identifying patients with de novo acute myeloid leukemia (AML) who will probably respond to the “7 + 3” induction regimen remains an unsolved clinical challenge. This study aimed to identify whether c-Myc could facilitate cytogenetics to predict a “7 + 3” induction chemoresponse in de novo AML.Methods: We stratified 75 untreated patients (24 and 51 from prospective and retrospective cohorts, respectively) with de novo AML who completed “7 + 3” induction into groups with and without complete remission (CR). We then compared Myc-associated molecular signatures between the groups in the prospective cohort after gene set enrichment analysis. The expression of c-Myc protein was assessed by immunohistochemical staining. We defined high c-Myc-immunopositivity as > 40% of bone marrow myeloblasts being c-Myc (+).Results: Significantly more Myc gene expression was found in patients who did not achieve CR by “7 + 3” induction than those who did (2439.92 ± 1868.94 vs. 951.60 ± 780.68; p = 0.047). Expression of the Myc gene and c-Myc protein were positively correlated (r = 0.495; p = 0.014). Although the non-CR group did not express more c-Myc protein than the CR group (37.81 ± 25.13% vs. 29.04 ± 19.75%; p = 0.151), c-Myc-immunopositivity could be a surrogate to predict the “7 + 3” induction chemoresponse (specificity: 81.63%). More importantly, c-Myc-immunopositivity facilitated cytogenetics to predict a “7 + 3” induction chemoresponse by increasing specificity from 91.30 to 95.92%.Conclusion: The “7 + 3” induction remains the standard of care for de novo AML patients, especially for those without a high c-Myc-immunopositivity and high-risk cytogenetics. However, different regimens might be considered for patients with high c-Myc-immunopositivity or high-risk cytogenetics.

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The Molecular ‘Myc-anisms’ behind Myc-Driven Tumorigenesis and the Relevant Myc-Directed Therapeutics

Cited by 15 publications

References 223 publications

Differential Expression of the TLR4 Gene in Pan-Cancer and Its Related Mechanism

Differential Expression of the TLR4 Gene in Pan-Cancer and Its Related Mechanism

p53/FBXL20 axis negatively regulates the protein stability of PR55α, a regulatory subunit of PP2A Ser/Thr phosphatase

Chemoresponse of de novo Acute Myeloid Leukemia to “7+3” Induction can Be Predicted by c-Myc-facilitated Cytogenetics

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