MYC Oncogene

The MYC gene encodes a phosphoprotein that plays a role in a variety of cellular processes, including the cell cycle, cell growth, apoptosis, and cellular metabolism. The gene is located in the long q arm of chromosome 8 and in the nucleoplasm of a cell. It belongs to the basic helix-loop-helix zipper class of transcription factors functioning in the developmental processes. It enforces DNA replication and entry into the S phase of the cell cycle by the expression of cyclins and represses kinases inhibitors p21 and p27.

Through checkpoints, it is restrained from causing tumorigenesis through proliferative arrest, apoptosis, and cell cycle arrest (or cellular senescence). In human cancer, it is frequently observed to be highly amplified, being one of the most amplified oncogenes compared to others.

Translocations involving the MYC gene are associated with Burkitt lymphoma, where cancer starts in immune cells called B-cells. The mutation results in the constitutive expression of MYC and cancer persists due to that sustained activation. Burkitt lymphoma is treated utilizing a number of chemotherapy drugs and an immunotherapy drug called rituximab, which targets the CD20 protein, causing the immune system to kill the marked cells. The combination is called chemoimmunotherapy and is a very intense treatment lasting several months. Burkitt lymphoma is one of the more curable forms of non-Hodgkin lymphoma, with a long-term survival rate of 60% to 90%.

As a transcription factor, MYC regulates and activates transcription through the binding of DNA sequences in promoters. MYC identifies as a proto-oncogene due to its multiple roles, participating in cellular functions that are related to growth and proliferation. The proteins MYC encodes function as parts of a normal cell’s growth-control pathway. The genes required for cell growth and proliferation would then be activated. As an oncogene, maintaining MYC at homeostatic levels is important for the normal function of the cell, regulated through phosphorylation. The sustained activation of MYC leads to the hallmarks of cancer, where it is overexpressed, leading to enhanced cell growth and avoiding its suppressors, therefore causing the next steps of cancer, including angiogenesis and inflammation.

Discussion & Future Directions

The MYC gene is an important regulator in the processes of the cell, but is has a central role in the oncogenic process, where it is present in many human cancers. MYC overexpression leads to the development and growth of tumors as it plays a role in the process of cell growth. Because of this, the inhibition of MYC would be a stronger approach for the treatment of many cancers, achieving a more desirable effect on the tumor, limiting or stopping its growth. However, MYC is challenging to directly target due to the drug resistance it has, leading to more exploration needed to stop the overexpression of MYC in malignant cells. By inhibiting the processes MYC is involved in, tumor growth can be treated from targeting this oncogene, either by inducing the regulation of MYC or inhibiting the transcription/translation of MYC itself.

Edward Zhuang