On October 7, the Nobel Assembly at the Karolinska Institute awarded the 2024 Nobel Prize in Physiology or Medicine to Victor Ambrose and Gary Ruvkun “for the discovery of microRNA and its role in post-transcriptional gene regulation”.

Victor Ambrose and Gary Ruvkun unexpectedly discovered microRNA, a molecule found in our cells, which has since provided scientists with valuable information about its role in cancer.

This discovery, made in 1993, has since been the foundation of many studies by scientists in genetic research, especially in the diagnosis and treatment of cancer.

What is microarna?

It’s all rooted in our genes. They are like instructions inside our body that tell our cells how to work. They tell your body what color your eyes should be, what your height should be or even how your body should fight disease.

Genes control how our body grows, develops, and functions every day. They are made up of DNA and determine our traits and what our personality will look like.

Deep inside the genes is DNA that acts like a blueprint that contains all the instructions about how our bodies work. RNA (ribonucleic acid), meanwhile, is a molecule that reads instructions from DNA and carries them out to make proteins.

Think of DNA as a recipe book, and RNA as a cook who follows recipes to make things.

But a type of RNA called microRNA is different. It has specific functions and too much of it can lead to serious conditions such as cancer, diabetes or autoimmunity.

MicroRNAs are single-stranded noncoding RNAs (ncRNAs) that are approximately 19–25 nucleotides long and are highly conserved throughout evolution.

They are a type of RNA (ribonucleic acid) that affect many complex functions in the body.

Unlike regular RNA, microRNA or miRNA does not make proteins itself, but it can stop or slow down the process by controlling how much protein is made. We now know that cells and tissues cannot function properly without microRNAs.

A step forward in gene regulation

In the late 1980s, Victor Ambrose and Gary Ruvkun studied a small roundworm, C. elegans, in the laboratory of Robert Horwitz. They focused on two genes, lin-4 and lin-14, which control how cells develop.

Ambrose found that lin-4 produced a small RNA that blocked lin-14. Ruvkun later discovered that Lin-4 prevented Lin-14 from making proteins.

This revealed a new way of regulating genes by microRNAs. Although initially ignored, further research proved that microRNAs exist in many organisms, including humans, and regulate gene activity. The biologists published their work in 1993 in the journal Cell.

This discovery was unexpected as it opened up a new dimension to gene regulation, which is essential for all complex life forms, including humans.

Biologists have discovered that when microRNA regulation goes wrong, it can lead to cancer, and mutations in the genes responsible for microRNAs have been linked to conditions such as congenital hearing loss, as well as eye and bone disorders.

Mutations in the key protein needed to make microRNAs cause DICER1 syndrome, a rare, serious condition associated with cancer in various organs and tissues.

How could Microna change cancer treatment?

While we know how microRNAs can influence cancer development, a recent study showed that the relationship is a bit complicated.

The way microRNAs work is complex. It interacts with other molecules such as long non-coding RNA, circular RNA, mRNA (messengerRNA), and proteins, as well as other microRNAs.

MicroRNAs don’t just work inside cells. It can also be released into body fluids and travel to other cells, acting like a chemical messenger. This ability to communicate between cells increases its effect on cancer.

Scientists revealed that microRNA could become a useful tool for diagnosing cancer. It is found in many body fluids, and several studies have shown that its presence is linked to cancer.

Because of this, microRNAs can be used as biomarkers, a signal that doctors can use to detect cancer early, predict how it will develop, and monitor its progress.

In bladder cancer, researchers created a model using three genes to predict how long a patient might live. In pancreatic cancer, they studied 24 tissue samples and found more than 57,000 individual cell types.

This helped them understand how certain cells interact with tumor-fighting immune cells. These findings could help improve cancer treatments by harnessing the immune system.

In addition to acting as biomarkers, microRNAs also show potential in cancer treatment.

In early research, scientists developed microRNA mimics and inhibitors to target specific microRNAs in cancer cells. Later, he worked on using nanoparticles to deliver these miRNA-based therapies directly to cancer cells, thereby improving the effectiveness of the treatments.

CAR-T therapy, a type of immune system therapy, has also been explored as a way to deliver microRNA-based drugs to tumors. CAR-T therapy is a treatment where a patient’s immune cells are modified to better recognize and attack cancer cells.

Drug resistance in cancer treatment

One of the biggest problems in cancer treatment is that cancer cells often become resistant to drugs. Recent studies have shown that microRNA plays an important role in this resistance.

Scientists are now looking for ways to target the microRNAs responsible for this resistance.

New technologies and approaches, such as using RNA technology, combining different treatments, or repurposing old drugs, are offering hope for overcoming drug resistance.

As the technology continues to improve, the potential applications of microRNAs in cancer treatment will continue to grow.