- MicroRNAs (miRNAs) are small non-coding RNAs, typically 20–24 nucleotides in length, that play a key role in the post-transcriptional regulation of gene expression by binding to the 3′ untranslated regions (3′UTRs) of target mRNAs, leading to their degradation or translational repression.
- In the context of epithelial-to-mesenchymal transition (EMT), miRNAs serve as crucial regulators that either promote or inhibit EMT by targeting EMT-inducing transcription factors, epithelial markers, and mesenchymal effectors.
- One of the most well-characterized families is the miR-200 family, which includes miR-200a, miR-200b, and miR-200c. These miRNAs inhibit EMT by directly targeting ZEB1 and ZEB2, two transcriptional repressors of E-cadherin, thereby maintaining epithelial identity.
- Conversely, certain miRNAs, such as miR-21 and miR-10b, are known to promote EMT by suppressing tumor suppressor genes or upregulating mesenchymal traits. For example, miR-21 targets PTEN and PDCD4, leading to activation of signaling pathways like PI3K/Akt that facilitate EMT. Additionally, TGF-β signaling, a major inducer of EMT, can modulate the expression of various miRNAs. It upregulates EMT-promoting miRNAs and downregulates epithelial-supporting ones, thereby reinforcing the transition at a post-transcriptional level.
- MicroRNAs act as fine-tuners of EMT, contributing to the plasticity and reversibility of the process, especially in development, wound healing, and cancer metastasis. In cancer, altered miRNA expression profiles often correlate with aggressive, invasive phenotypes, and resistance to therapy. For example, reduced miR-200 expression is frequently observed in metastatic tumors, where EMT is active, while miR-34a, another tumor-suppressive miRNA, can inhibit Snail expression and suppress EMT-associated traits.
- Overall, miRNAs serve as powerful modulators of EMT, functioning in a highly context-dependent manner to regulate the balance between epithelial stability and mesenchymal transition. Their role offers potential diagnostic and therapeutic value, as miRNA signatures may predict EMT status or serve as targets to reverse mesenchymal phenotypes in disease.
