on November 03, 2026
MicroRNA: small regulators with an important role in cancer
Cancer research is progressively shifting its focus towards the tumor microenvironment, epigenetic regulation, and the molecules that control gene expression.
Among these molecules, microRNAs (miRNAs) occupy a special place. They are small non-coding RNAs, generally consisting of about 20–24 nucleotides. They do not directly produce proteins, but regulate the expression of numerous genes at the post-transcriptional level by binding to messenger RNAs and promoting their degradation or reducing their translation.
Their interest in oncology stems primarily from their ability to simultaneously influence several biological processes. The dysregulation of certain miRNAs can be associated with cell proliferation, apoptosis, angiogenesis, invasiveness, epithelial-mesenchymal transition, and the maintenance of tumor cell characteristics.
Some miRNAs can behave as oncogenes, promoting tumor progression, while others exert a tumor-suppressive function. Their significance depends on the type of tumor, the tissue involved, and the genes on which they act.
The material examined highlights precisely this characteristic: changes in miRNA expression can accompany neoplastic transformation and potentially represent possible disease biomarkers.
When microRNA becomes part of the problem
The complexity of tumors also stems from the fact that a single molecular alteration is rarely sufficient to explain the entire evolution of the disease.
A single microRNA can control numerous genes simultaneously, and at the same time, multiple microRNAs can converge on the same intracellular circuits.
This makes the system extremely complex.
In cancer, a microRNA normally responsible for limiting proliferation may be reduced, while a microRNA with oncogenic activity may be overexpressed. The result can be a shift in the balance between cell proliferation and death.
One particularly studied example is miR-21, which is frequently increased in several tumors. In glioblastoma, its relationship with the Wnt/β-catenin/TCF4 pathway, a signaling network involved in cell proliferation and survival, has been studied.
This relationship is particularly interesting because it can interact with the response to pharmacological therapy.
Sulforaphane and miR-21: an experimental model of sensitization
Among the plant compounds most studied in this field is sulforaphane, an isothiocyanate derived mainly from Brassicaceae.
In the experimental glioblastoma model, sulforaphane reduced miR-21 expression by inhibiting the Wnt/β-catenin/TCF4 pathway. The reduction of miR-21 was associated with increased temozolomide-induced apoptosis.
This finding is interesting because it does not simply suggest a cytotoxic effect of the plant compound, but shows a possible intervention in a molecular circuit involved in the response to treatment.
However, it is essential to emphasize the level of evidence: these are results obtained mainly in tumor cells and animal models. They do not demonstrate that dietary sulforaphane can treat glioblastoma in humans.
The difference between these two statements is substantial.
Research can identify a very interesting biological mechanism without it yet having become a clinically effective therapy.
From microRNA to epigenetics
Interest in plant compounds does not only concern microRNAs.
Many phytochemical substances have been studied for their ability to interfere with various levels of epigenetic regulation, including DNA methylation, histone modifications, epigenetic enzyme activity, and non-coding RNA regulation.
The material analyzed cites, among others, curcumin, EGCG, polydatin, sulforaphane, genistein, indole-3-carbinol, and quercetin.
This characteristic makes research on phytochemicals particularly interesting because cancer is not merely the result of an isolated genetic mutation: it is also the result of a complex reorganization of cellular programs.
In this context, a substance capable of simultaneously modifying multiple signaling pathways could theoretically intervene at different nodes of the tumor network.
But precisely this multiple action makes an in-depth study of pharmacology, bioavailability, and possible interactions with cancer treatments necessary.
The pancreas and the role of miR-15a
Another particularly interesting example concerns the microRNA miR-15a in pancreatic ductal carcinoma.
Research published in 2024 showed that the reduction of miR-15a is associated with the activation of a molecular circuit involving Fra-2, IGF1R, and mTOR. Under nutrient-deprived conditions, typical of the unique pancreatic carcinoma microenvironment, this circuit can contribute to the ability of tumor cells to maintain growth and metabolic adaptation.
This finding is particularly significant because it highlights how important it is to consider the tumor in its biological environment.
A neoplastic cell does not live under normal conditions: it may be in a tissue characterized by hypoxia, nutrient deficiency, fibrosis, and alterations in signals from surrounding cells.
MicroRNAs can contribute to adaptation to these conditions.
In the case of miR-15a, experimental research therefore indicates a possible role in regulating the metabolism and response to nutritional stress of pancreatic cancer.
When microRNA research meets therapy
The possibility of directly using microRNAs as therapeutic tools is one of the most interesting prospects of cancer research.
In theory, one could try to restore a microRNA suppressed in the tumor or reduce an oncogenic microRNA.
The problem is that microRNAs are delicate biological molecules. Their degradation, distribution in the body, the difficulty of selectively reaching the tumor, and the possibility of interfering with numerous genes represent major obstacles.
The material examined highlights precisely these limitations, including instability, short half-life, unfavorable pharmacokinetics, and lack of selectivity.
Research is therefore evaluating increasingly sophisticated strategies to achieve targeted modulation of the circuits regulated by microRNAs.
Curcumin and chemoresistance in pancreatic cancer
Curcumin, the main polyphenol of Curcuma longa, represents another example of a plant substance studied in the context of drug resistance.
An experimental study on pancreatic carcinoma observed that curcumin can increase the sensitivity of gemcitabine-resistant cells through the modulation of the PRC2-EZH2-PVT1-c-Myc axis. Modifications associated with spheroid formation and tumor stem cell characteristics were also observed. The results were subsequently observed in an animal xenograft model.
However, in this case too, the level of evidence must be stated precisely.
This is not a clinical trial demonstrating that curcumin, taken as food or a supplement, increases the survival of patients with pancreatic carcinoma.
This is preclinical evidence, useful for identifying a possible biological mechanism and generating new therapeutic hypotheses.
This transition from laboratory research to clinical practice requires pharmacokinetic, safety, interaction, and dosage studies, and above all, controlled clinical trials.
An important point: not all studies have the same value
Research on phytochemicals and microRNAs is extremely dynamic, but precisely for this reason it requires critical reading.
A result obtained in a cell line is not equivalent to a result obtained in an animal.
A result obtained in an animal is not equivalent to a clinical benefit in humans.
And an association observed in a patient does not necessarily demonstrate a causal relationship.
This distinction becomes even more important when talking about natural substances, because the term "natural" does not automatically mean "therapeutic", "safe", or "free of interactions".
Bioavailability also represents a central problem. A concentration capable of modifying a microRNA in a cell culture may be much higher than that achievable in tissues through normal diet.
For this reason, preclinical results must be interpreted as tools for understanding mechanisms and identifying new research directions, not as a demonstration of therapeutic efficacy.
Future research: from nutrition to signaling medicine
The true interest of microRNAs may lie in the possibility of better understanding how the biological environment influences cellular behavior.
Diet, metabolism, inflammation, oxidative stress, and signals from the microenvironment can interact with an extremely complex network of gene regulation.
Phytochemicals from plants represent one of the tools through which research is trying to study this network.
Sulforaphane, curcumin, EGCG, and other polyphenols should therefore not be presented simply as "natural anti-cancers". It is more correct to consider them bioactive molecules capable, in experimental models, of interfering with specific cellular circuits, some of which include microRNAs and epigenetic systems.
This is a very different and scientifically more solid perspective.
From prevention to personalization
The evolution of microRNA research could contribute, in the future, to increasingly personalized cancer medicine.
If specific miRNA profiles manage to distinguish tumor subtypes, predict drug response, or identify certain biological changes early, these small RNAs could become part of increasingly sophisticated diagnostic and prognostic systems.
In parallel, the study of phytochemicals could contribute to the identification of molecules capable of interfering with specific altered pathways.
The decisive step will, however, be the transition from biological plausibility to clinical demonstration.
It is precisely in this space that a vision of Integrated Medicine can become interesting: not replacing cancer therapy with phytotherapy, but studying how diet, lifestyle, and bioactive substances can be incorporated, when appropriate and under professional supervision, into a personalized pathway.
Personalization does not mean choosing a plant because it "fights cancer". It means understanding the person's biological context, ongoing therapies, nutritional status, possible interactions, and available evidence.
MicroRNA: small signals, great prospects
MicroRNAs represent one of the most fascinating systems through which the cell controls gene expression.
Their alteration can participate in fundamental processes of carcinogenesis, from proliferation to apoptosis, from angiogenesis to invasive capacity and epithelial-mesenchymal transition.
Research on plant compounds suggests that some bioactive molecules can modulate part of these circuits.
Sulforaphane represents a particularly interesting experimental example regarding its relationship with miR-21 and the response to temozolomide; curcumin, on the other hand, offers a model for studying chemoresistance in pancreatic carcinoma through epigenetic circuits and regulators of tumor stemness.
But the scientifically correct perspective is not that of replacing cancer therapies with plants.
It is that of continuing to study how bioactive molecules interact with tumor biology, to understand if and when they can become truly useful complementary tools.
The distance between an interesting mechanism and an effective therapy remains large. And it is precisely clinical research that must establish whether that distance can truly be bridged.
Bibliographic references
1. Sulforaphane enhances temozolomide-induced apoptosis because of down-regulation of miR-21 via Wnt/β-catenin signaling in glioblastoma. Journal of Neurochemistry, 2015, 134:811-818.
2. Curcumin sensitizes pancreatic cancer cells to gemcitabine by attenuating PRC2 subunit EZH2, and the lncRNA PVT1 expression. Carcinogenesis, 2017, 38:1036-1046.
3. Nutrient restriction-activated Fra-2 promotes tumor progression via IGF1R in miR-15a downmodulated pancreatic ductal adenocarcinoma. Signal Transduction and Targeted Therapy, 2024, 9:31.
4. 5-FU-miR-15a Inhibits Activation of Pancreatic Stellate Cells by Reducing YAP1 and BCL-2 Levels In Vitro. International Journal of Molecular Sciences, 2023, 24:3954.
