Introduction: Cancer, a global health crisis, is increasingly being understood through the lens of epigenetics and mRNA dysregulation. mRNA (messenger RNA) is the conduit of genetic information from DNA to the cellular machinery, influencing crucial processes such as growth, division, and apoptosis. Abnormalities in mRNA expression and stability can lead to cancer by activating oncogenes or suppressing tumor suppressor genes. The potential impact of understanding how epigenetic modifications influence mRNA pathways is immense, offering new avenues for cancer prevention and treatment. This potential should inspire and motivate us to continue our research.
Methods: This review analyzes studies from 2016 to 2024 from databases such as PubMed, Google Scholar, and ScienceDirect. It focuses on how mRNA dysregulation, driven by epigenetic changes, contributes to cancer progression. The investigation covers how alterations in mRNA expression, stability, and translation affect key cellular pathways involved in tumor development alongside therapeutic strategies targeting these processes.
Results: Dysregulated mRNA expression and epigenetic alterations synergistically promote cancer progression. For instance, increased mRNA levels of Cyclin D1, driven by histone acetylation, can lead to uncontrolled cell division, a hallmark of cancer. Conversely, reduced stability of tumor suppressor mRNAs, such as p16INK4a, allows cancer cells to evade apoptosis. Hypermethylation of the p16INK4a promoter silences its expression, facilitating tumor growth.
Epigenetic mechanisms significantly influence mRNA dynamics. DNA methylation can silence tumor suppressor genes, reducing their mRNA production. For example, the hypermethylation of p16INK4a leads to its loss of function, contributing to unchecked cell proliferation. Histone modifications may open or close chromatin, either facilitating or hindering the transcription of critical genes.
Additionally, non-coding RNAs, including microRNAs and long non-coding RNAs (lncRNAs), play crucial roles in regulating mRNA stability and translation. Dysregulated microRNAs, such as miR-21, can destabilize tumor-suppressing mRNAs like PTEN and PDCD4, enhancing cell survival and contributing to cancer progression. On the other hand, lncRNAs like HOTAIR can stabilize oncogenic mRNAs, such as VEGF, promoting tumor growth and metastasis.
Emerging studies suggest that targeting mRNA stability and translation—through pharmacological agents or lifestyle interventions like diet and exercise—could reduce cancer risk. For instance, epigenetic therapies, including histone deacetylase inhibitors and DNA methyltransferase inhibitors, have shown promise in restoring standard mRNA expression patterns and potentially limiting cancer proliferation. These interventions may correct dysregulated pathways, offering a novel cancer prevention and treatment approach.
Conclusion: mRNA dysregulation, influenced by epigenetic factors, is pivotal in cancer progression. Cancer cells can circumvent normal growth controls by altering mRNA expression and stability. The interplay between epigenetics and mRNA presents promising therapeutic avenues, emphasizing the need for further research. Targeting mRNA pathways alongside epigenetic modifications could lead to innovative strategies for cancer prevention, early detection, and treatment, ultimately improving patient outcomes.