Role of Tumor Suppressors in Prostate Cancer
Abstract
Micro-RNAs are small RNA molecules that are well conserved in animals and plants, suggesting that they have an important role in cell growth and cell death (their discoverers received the Nobel Prize). Nearly 2,500 micro-RNAs were discovered and the functions of many micro-RNAs were also revealed. Each micro-RNA binds to specific messenger RNA (which codes for proteins) and inhibits the expression of proteins. Mature micro-RNAs are originated from large RNA molecules by processing the large RNA in two steps. Researchers made a breakthrough finding that larger RNA molecules (from which mature micro-RNAs are made) actually code for very small proteins, miPEPs (published in the prestigious journal, Nature) in plant cells. These small proteins are called peptides. They have shown that these small peptides (miPEPs) control the expression of mature micro-RNAs, which control the expression of proteins of interest. In brief, these small peptides are master regulators that control the expression of cancer proteins. Recently, it was shown that a micro-RNA (called miR-24) functions as a prostate cancer metastatic inhibitor/suppressor. They have shown that this micro-RNA (miR-24) inhibits the expression of prostate cancer metastasis-inducible genes. Based on the breakthrough finding described above, we hypothesized that a large RNA molecule (a precursor of micro-RNA miR-24) may code for small peptides (called miPEP-24) and that these peptides function as prostate cancer metastatic inhibitors/suppressors. Loss of expression of these peptides (seen in the case African Americans) leads to a selective advantage for the prostate cancer cells to metastasize in Black Americans compared to White Americans. To test this hypothesis, we have cloned the gene that codes for miPEP-24. We will test whether these peptides have prostate metastatic suppressor activity on a variety of prostate cancer cells and identify the mechanism by which it regulates prostate cancer metastasis. Since loss of expression of these peptides in prostate cancer cells suggest that prostate cancer cells are undergoing metastasis, one can use this as a biomarker for the early detection of prostate cancer metastasis. Therefore, this will be first immediate outcome of this research project that will help millions of prostate cancer patients. Furthermore, these results will also provide novel biomarkers for the early detection of metastasis of other cancers, as the loss of miR-24 was shown to be responsible in other cancers. In future, pri-miRNA-encoded peptides signatures will be tested as novel clinical biomarkers for further subtyping of prostate cancer and their potential for predicting metastasis. In addition, these peptides can be easily synthesized and can be used as prostate cancer metastatic suppressors and to target prostate cancer metastatic cells. If our results are positive, it will be highly encouraging to study in future whether synthetic peptides (miPEP-24) can be used as therapeutic agents to target prostate cancer metastatic cells in clinical trials to treat prostate cancer metastatic patients. In fact, one can modify the synthetic peptides and test them for more efficient therapeutic agents. Thus, our research will revolutionize the early diagnosis and treatment of metastatic prostate cancer and also other cancers and diseases. If our hypothesis is true, it will have a major impact in the fundamental biology that precursors of micro-RNA encoded peptides exist in mammalian cells (like in the case of plant cells), and this novel finding may open doors to new investigations such as biomarkers and therapy of all human cancers and diseases. This finding may be as important as the discovery of miRNA. Thus, we believe strongly that our research may change the landscape of the cancer field.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310294
Entities
People
- E. Shyam Reddy
Organizations
- Morehouse School of Medicine
- United States Army