On October 7, 2024, the Nobel Prize in Physiology or Medicine was awarded to American scientist Victor Ambros and American biologist Gary Ruvkun. They were recognized for their discovery of microRNAs (miRNAs) and their role in post-transcriptional gene regulation. This discovery has significant implications for understanding gene expression mechanisms, including in liver diseases.RNAs serve diverse functions, with one of the key roles being to guide protein synthesis, which is fundamental to life. MicroRNAs are a class of endogenous non-coding RNAs that play a crucial role in regulating gene expression. These small RNA molecules are about 22 nucleotides in length and exert their regulatory effects by degrading or inhibiting the translation of target messenger RNAs.
The function of miRNAs was first discovered in the model organism Caenorhabditis elegans. Traditionally, gene regulation was understood through the central dogma of biology, where DNA is transcribed into RNA and then translated into proteins. However, miRNAs revealed additional layers of regulation, where they interfere with the RNA-protein translation process. Their role in gene expression and subsequent protein malfunction links miRNAs to various diseases, including liver disorders.
MicroRNAs and Liver Diseases
- Regulation of Liver Fibrosis Progression by miRNAs Several miRNAs have been identified to play significant roles in the activation of hepatic stellate cells (HSCs), a key step in liver fibrosis. MiRNAs such as miR-21, miR-29, miR-708, miR-101, miR-455, miR-146, and miR-193 exhibit altered expression during HSC activation. By regulating molecules related to fibrosis signaling pathways and transcription factors, these miRNAs control the transdifferentiation, proliferation, apoptosis, and autophagy of HSCs. This makes them critical mediators in the progression of liver fibrosis and key targets for therapeutic intervention.
- miRNAs as Diagnostic Tools for Liver Diseases MiRNA expression profiles undergo significant changes during disease states, showing high specificity. Different tumors exhibit distinct miRNA expression patterns that reflect the type of cancer. For instance, in hepatocellular carcinoma (HCC), miR-767-5p and miR-1180-3p are markedly upregulated, demonstrating strong specificity. This makes miRNAs promising biomarkers for diagnosing liver diseases, offering new pathways for early detection and personalized treatment strategies.
- miRNAs as Therapeutic Targets for Liver Diseases Due to their dual roles in oncogenes and tumor suppressor genes, synthetic miRNA mimics or antagonists are being developed as cancer therapies. In prior research, an inactivated adenovirus was used to introduce miR-22 into the body, which inhibited liver cancer progression. When compared to anti-angiogenic drug lenvatinib, miR-22 therapy demonstrated a longer survival time with no observed toxicity. Currently, anti-miRNA therapies, such as those targeting miR-122, have reached Phase II clinical trials.
Conclusion
The discovery of miRNAs has uncovered new dimensions of gene regulation and opened avenues for treating complex diseases like liver disorders. With the advancement of technology, miRNAs hold promise in medicine, agriculture, and biotechnology. In the future, miRNA-based therapies may become key components of personalized and precision medicine, offering breakthrough progress in human health.
