MYC oncogene
The MYC oncogene, also known as c-Myc, is a crucial transcription factor that plays a significant role in regulating various biological processes, including cell proliferation, growth, and differentiation. It is part of a family of related genes, including l-myc and n-myc, and is essential for the expression of numerous target genes by binding to specific DNA sequences known as enhancer boxes (E-boxes). In healthy cells, MYC expression is tightly controlled and occurs mainly in actively dividing cells. However, genetic alterations can lead to its aberrant activation in cancer, affecting over 70% of human tumors such as breast, colon, and various hematological cancers.
The role of MYC in cancer biology is profound, as its dysregulation is associated with numerous malignancies and is linked to a significant number of cancer-related deaths annually in the United States. Given its centrality in tumor growth, MYC is considered an attractive target for cancer therapies. Research is ongoing to develop strategies for inhibiting MYC, including various molecular techniques and therapeutic approaches aimed at disrupting its function and expression. These efforts may enhance the effectiveness of current cancer treatments and provide new avenues for combating cancer influenced by MYC.
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Subject Terms
MYC oncogene
ALSO KNOWN AS: c-Myc, v-myc myelocytomatosis viral oncogene homolog (avian)
DEFINITION: First identified in humans based on its homology to the chicken viral oncogene (v-myc), MYC belongs to a family of MYC genes that codes for a transcription factor containing the basic-helix-loop-helix Leucine zipper (bHLH/LZ) domain. The MYC family included three related human genesc-myc, l-myc, and n-myc. The MYC proteins bind to the enhancer box (E-box) sequence and activate the expression of more genes. By modifying the expression of its target genes, MYC can activate numerous biological effects. It affects cell proliferation (downregulates CDKN1A, or p21), regulates cell growth (upregulates TP53), induces apoptosis (upregulates BCL2), and regulates differentiation (downregulates C/EBPA).
Role in cancer biology: The role of MYC in influencing critical aspects of the cell cycle machinery makes it a centerpiece and key to the enigma of cancer biology. In normal cells, MYC expression is under tight regulation, with the gene being expressed only in actively dividing cells. In contrast, genetic aberrations result in the uncontrolled expression of MYC in cancer cells. Aberrant expression of MYC plays a significant role in more than 70 percent of human cancers, includingbreast cancer, colon cancer, gynecological cancer, hepatocellular carcinomas, and a variety of hematological tumors possessing abnormal MYC signatures. An estimated 70,000 cancer deaths per year in the United States are associated with changes in the c-MYC gene or its expression. The clinical significance of MYC gene alterations in human cancers is best illustrated by the amplification of MYCN (N-myc) in neuroblastoma and the translocation of MYC from its normal position on chromosome 8 to chromosome 14 in Burkitt lymphoma.
Inhibiting MYC: Experimental evidence shows that inhibiting MYC significantly halts tumor cell growth and proliferation. Consequently, MYC is an attractive target for cancer therapy. Another advantage of MYC as a therapeutic target is that it is downstream of multiple converging signaling pathways affected by mutations in several genes in different cancer types. Significant advances in drug development aimed at eliminating MYC include targeting it by antisense mitochondrial ribonucleic acid (mRNA) and deoxyribonucleic acid (DNA) oligonucleotides, triple-helix-forming oligonucleotides, ribozymes, porphyrins, and small interfering RNA (siRNA). Inhibition of MYC can be achieved with many of these approaches. However, for increased clinical efficacy, it is probable that intervention, possibly in combination with traditional chemotherapy, will be necessary.
Alternative approaches to targeting MYC include developing medications that target the gene transcription process, inhibiting the translation of MYC mRNA, and using synthetic lethality to kill MYC-dependent cells selectively.
Bibliography
Dhanasekaran, Renumathy, et al. “The MYC Oncogene - The Grand Orchestrator of Cancer Growth and Immune Evasion.” Clinical Oncology, vol. 19, no. 1, 2022, pp. 23-36. doi:10.1038/s41571-021-00549-2.
Vlahopoulos, Spiros, et al. “OGG1 as an Epigenetic Reader Affects NFκB: What This Means for Cancer.” Cancers, vol. 16, no. 1, 28 Dec. 2023, doi:10.3390/cancers16010148.
Stasevich, Ekaterina M., et al. “The Role of Non-Coding RNAs in the Regulation of the Proto-Oncogene MYC in Different Types of Cancer.” Biomedicines, vol. 9, no. 8, 30 July 2021, doi:10.3390/biomedicines9080921.
Wolf, Elmar, and Martin Eilers. "Targeting MYC Proteins for Tumor Therapy." Annual Review of Cancer Biology, vol. 4, 2020, pp. 61-75. doi.org/10.1146/annurev-cancerbio-030518-055826.
Sabo, Arianna, et al. "Selective Transcriptional Regulation by Myc in Cellular Growth Control and Lymphomagenesis." Nature, vol. 24, no. 511, July 2014, pp. 488–92. doi:10.1038/nature13537.