Scientists reveal how miRNAs shape cancer and offer new pathways for treatment

Groundbreaking research reveals the role of miRNAs in driving cancer, while offering innovative diagnostic tools and treatments, including solutions to chemotherapy resistance.

Study: miRNA interaction: Mechanisms and therapeutic interventions in cancer. Image credit: Shutterstock AI / Shutterstock.com

A recent review published in the journal MedComm Oncology describes how microRNAs (miRNAs) interact to cause cancer and their potential role in the diagnosis and treatment of this disease.

What are miRNAs?

The first miRNA was discovered in 1993 Caenorhabditis elegansa widely used animal model, and has since been detected in both plants and animals.

After being synthesized as primary miRNAs, miRNAs are processed to become mature functional miRNAs. Functional miRNAs are found in both introns and exons of non-coding RNAs (ncRNAs) and introns of pre-RNAs.

The main activity of miRNAs is to inhibit the translation of messenger RNA (mRNA) either by cleaving the mRNA or by binding to the 3′ untranslated region (3′ UTR) of a target RNA molecule to repress the expression of protein-coding genes. In fact, miRNAs post-transcriptionally regulate over 60% of human protein-coding genes and regulate all aspects of the cell cycle from development to differentiation and apoptosis.

The role of miRNAs in cancer development

Dysregulation of miRNAs can lead to cancer, as these molecules regulate specific genes involved in cell proliferation, apoptosis, migration and invasion.

Many miRNAs leave the cell via exosomes, carriers such as argonaut proteins (AGOs), and multiple other pathways to reach target cells and prevent mRNA repression. In addition, miRNAs interact with each other, facilitate intercellular communication, and act on immune cells. These interactions are actively involved in creating the tumor microenvironment that promotes tumor growth, as well as immune evasion, invasion and metastasis.

Inter-miRNA interactions are currently being investigated through high-throughput RNA sequencing (RNA-Seq), such as PANDORA-seq and Nanopore MinION RNA-Seq. Imaging technologies, including single-molecule imaging and cryo-electron microscopy, can also provide important insights into the dynamic interactions between miRNAs.

Advances in miRNA detection techniques

Notable advantages of miRNAs as biomarkers include their stability, presence in body fluids, fluid biopsiability, and specificity. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis is mainly used to detect exosomal miRNA. However, RNA-Seq, microfluidics, and next-generation sequencing (NGS) can also be used for miRNA diagnostic purposes.

Bioinformatics identifies targetable miRNAs from large-scale gene expression studies. Gene editing technologies such as CRISPR/Cas9 can also be used to validate and validate miRNA responsive elements (MREs) and improve the specificity of miRNA detection for point-of-care testing (POCT).

Other amplification techniques, besides qRT-PCR, can increase detection sensitivity at constant temperature. Nanoparticle-based miRNA detection is another promising area.

Bioinformatics can be combined with computational techniques to predict how certain miRNAs will function. Combining these computational data with experimental information can improve the prediction accuracy of miRNA interactions while also revealing unknown correlations between regulators and target molecules.

miRNAs as a therapeutic tool in cancer treatment

Currently, researchers are investigating the efficacy of miRNA nanoparticles and chimeric antigen receptor (CAR) T-cells as miRNA vehicles for targeted therapy. However, additional research is needed to determine how and why miRNAs change in different conditions.

In addition, miRNAs are involved in immunotherapy responses as they act directly on cancer cells, regulate immune checkpoint molecules, improve response to other immunotherapeutic agents, and optimize immune responses by their effects on immune cells and receptors.

The presence of miRNAs in the tumor microenvironment suggests their potential for synergistic immunotherapy, as they may improve the efficacy of these therapies while preventing immune rejection. However, additional studies are needed to advance these applications for clinical use.

Newer delivery systems such as nanotechnology offer new applications, including diagnostic and therapeutic tools such as miRNA nanoparticle biosensors and drugs. Nanotechnology improves drug bioavailability, specificity and efficacy of miRNAs.

Currently, several miRNA drugs are being investigated in preclinical and early clinical trials, including mimetics and inhibitors.

Overcoming chemotherapy resistance with miRNAs

Acquired drug resistance can arise in previously susceptible tumor populations, ultimately leading to chemotherapy failure and tumor recurrence. Chemotherapy resistance has a significant negative impact on both prognosis and survival of cancer patients, accounting for over 90% of cancer patient mortality.

Chemotherapy resistance within cancer cells has been attributed to various genetic, epigenetic, transcriptional and proteomic processes. For example, aberrant miRNAs can exacerbate cancer progression by interfering with epigenetic methylation, transcription factor dysregulation, and altering miRNA biogenesis.

Conversely, miRNAs can be used to predict and overcome drug resistance in cancer chemotherapy. For example, miR-21 expression has been associated with both breast cancer invasiveness and resistance to chemotherapy.

conclusions

A deeper understanding of miRNA mechanisms in cancer is crucial for the development of new diagnostic tools and therapeutic strategies.”

Additional research is needed to expand the applications of miRNAs in cancer diagnosis and treatment. This will likely include improving the sensitivity and specificity of detection and the stability and specificity of therapeutic targeting. These developments will support the inevitable adaptation of miRNAs to cancer precision medicine strategies.