Genes have been a focus of many scientific studies. When two scientists, Edward Tatum and George Beadle, experimented with bread mold fungus in 1941, they came up with the one gene, one enzyme hypothesis. Over time, this has evolved to a one gene, one protein hypothesis, and laid a crucial foundation for future studies. However, as researchers continued to study genes, it became clear that this area of study is much more complex. Recent studies have suggested that non-coding RNA, or rather a dysfunction in the ncRNA network, may have stronger links to disease pathology than previously believed.
What is ncRNA and How Does it relate to Disease?
Research into genetics and DNA is a complex topic. Improvements in technology over the years have allowed researchers to get a better view into genes, DNA, and RNA. In the 1950s, the first non-coding RNAs, or ncRNAs, were discovered. This included the identification of both transfer RNA, or tRNA, and ribosomal RNA, or rRNA [1].
Following these discoveries, researchers continued to look at ncRNA, the different classes, and how they affect the body. This led to the discovery of more ncRNA classes, including:
- Small nuclear RNAs (snRNAs)
- Small nucleolar RNAs (snoRNAs)
- lncRNAs
By the early 2000s, next-generation sequencing became a standard tool used in genetic research, allowing researchers to discover and understand ncRNA at a more rapid rate.
This also led to the discovery of a relationship between ncRNA network dysfunction and disease pathology.
Fast forward to the modern day, and researchers now have a much better understanding of how ncRNA relates to disease and health in general. There are numerous connections between non-coding RNA and various illnesses. A thorough understanding of these relationships is essential before examining how research is now linking ncRNA network dysfunction to disease pathology.
First of all, knowing how ncRNAs affect genes is crucial. They have an impact on gene regulation. In particular, lncRNAs, miRNAs, and circRNAs are the main non-coding RNA genes that play a role in gene expression. This means these are RNA sequences that have an impact on how genes are expressed, and as such, this can affect the development and functioning of cells in the human body.
This is also where the issue with a malfunction of ncRNAs comes into the picture. When these non-coding RNAs malfunction, it can ultimately affect how a person’s genes are expressed. In turn, this may potentially contribute to both the development and the progression of certain diseases.
It’s also crucial to realize that ncRNAs don’t work completely on their own. In fact, this is why the focus of this piece is on ncRNA network dysfunction. ncRNAs form a comprehensive network in the body. They interact with various molecules, which means there is constant cross-communication that happens within this network.
Latest Research on ncRNA Network Dysfunction and Disease Pathology
Researchers are starting to focus on diving deeper into the ncRNA networks in the human body, and how a dysfunction in these systems could be linked to certain diseases. There has been a particular focus on identifying the role of ncRNA network dysfunction in neurological, cardiovascular, and autoimmune diseases. Additionally, several studies have also looked at the connection this type of dysfunction may play in cancer.
ncRNAs and Neurological Conditions
A research paper published in the MDPI Journal of Cells [2] explored the current evidence linking non-coding RNAs to both neuropsychiatric and neurological disorders. Now, something to keep in mind here is that, unlike other kinds of RNA molecules, ncRNAs do not encode proteins. This is one of the major differences between them.
The paper connects microRNAs, or miRNAs, in particular, to certain neurological and neuropsychological conditions. This was discovered after carefully monitoring specific miRNA molecules to identify their targets and consider the potential molecular events that could be affected. In turn, the paper was able to make connections between these miRNAs and specific conditions, including:
- Cognitive decline: miR-132, miR-124, and miR-137.
- Neurodegeneración: miR-132, miR-124, miR-9.
- Neurological disorders: miR-155.
- Stroke: miR-132, miR-124.
They also found links between a dysfunction of certain miRNAs and glioblastoma, cerebral ischemia, Huntington’s disease, ALS, and other neurological problems.
A systematic review also looked closer at the link between ncRNAs and how they affect neurodevelopmental disorders [3]. The focus was to identify more precisely the role that ncRNAs play in the pathogenesis, diagnosis, prognosis, and treatment of these neurodevelopmental disorders.
Among the studies included in this systematic review, 32 had human subjects as part of the tests performed. Others recruited animals, and there was one study that focused on cells. Autism was a large focus among the studies included in this review, which is a type of neurodevelopmental disorder that is becoming an increasing concern in the modern day. There were also studies that focused on intellectual disability, attention-deficit hyperactivity disorder, learning disabilities, and Prader-Willi Syndrome.
There were a couple of patterns that the researchers identified during their review. Dysregulations in certain ncRNAs popped up frequently among individuals with Autism, for example. These disregulations affected a number of different ncRNAs, such as AQP4-AS1, Hsa-miR-657, hsa-piR-28059, and IFNG-AS1. This provided concrete evidence that a strong relation exists between Autism and ncRNA network dysfunction. Previously, we mentioned that ncRNAs form a complete network in the body. Dysregulations in one part can have a potential impact on another area, which is why different molecules have been associated with this neurodevelopmental disorder.
There were also several ncRNA dysfunctions the researchers identified in patients with ADHD, learning disabilities, and other neurodevelopmental problems.
ncRNAs and Cardiovascular Disease
Heart disease is considered a major public health problem. It’s often also named the number one killer among the general population. The World Health Organization reports that about 19.8 million individuals died due to cardiovascular diseases in 2022 [4]. Heart attack and stroke were the most common reasons for mortality among these cases.
More research is showing a strong link between the dysregulation of the ncRNA network and the development of cardiovascular diseases. This is particularly due to the effect of ncRNAs on gene expression related to cardiovascular health.
When the ncRNA network is dysfunctional, there are several complications that can develop. Research published in the AHA|ASA Journals [5] provides a comprehensive explanation of how this connects to hypertension. Individuals with high blood pressure have been found to show dysfunction of certain ncRNAs in their bodies.
Hypertension is considered a critical risk factor for cardiovascular disease. When blood pressure remains high consistently, it puts pressure on the arteries and blood vessels. The heart works harder to pump blood through the body. This causes long-term damage that might develop gradually, but can have a significant impact on the functioning of the cardiovascular system.
Long non-coding RNAs, also known as lncRNAs, have also been found to hold a link to heart failure. This is another serious cardiovascular condition that can reduce the amount of blood that reaches certain parts of the body. In particular, one study [6] found that the role of long non-coding RNAs in cardiac disease is specifically related to their impact on gene transcription and translation, as well as modifications that occur after the initial translation process.
Dysfunctions in these non-coding RNAs can impact how they affect the expression of genes in the cardiovascular system. When this happens, cellular functions can become impaired, thus potentially contributing to congestive heart failure.
ncRNA Network Dysfunction and Cancer
Another important connection made between dysfunction of the ncRNA network and the human body is the risk of cancer. It is well-known that cancer is largely connected to genetic mutations, environmental factors, inherited factors, and more. As more discoveries are made regarding these non-coding RNA molecules, it’s becoming clear that they also play a role in cancer.
Disruptions in the normal functioning of non-coding RNA can cause problems with how cells function. They can interfere with the metabolism, growth, and apoptosis of cells. It has been found that some ncRNAs play a role in suppressing the development of cancer, which develops when cells begin to divide and function abnormally. Problems with how these ncRNAs affect the expression of genes can thus affect their ability to suppress the growth of cancer.
Additionally, researchers are also turning their focus to how ncRNA might become an ideal target in cases where patients experience resistance to cancer drugs. When cancer drugs are unable to provide efficient treatment, the cancer begins to spread and advance. This increases the complications associated with cancer and makes the prognosis seem more negative for the patient.
By targeting ncRNA in cancer drug resistance [7], researchers are hoping to find how these therapeutic targets might help to enhance the way medications work. The main aim here is to find out whether turning to ncRNA as a therapeutic target can ensure the pharmaceuticals used in cancer drugs reach and work on the cancerous cells.
It is important to note that there is a two-way connection when looking at ncRNA. It’s not as simple as turning to these as therapeutic targets. Some ncRNAs may also contribute to the development of resistance to chemotherapy drugs. This, however, opens up further opportunities for researchers, as suppressing these ncRNAs becomes a new potential way to address this effect.
The role of ncRNA in cancer goes beyond only treatments and reducing the impact of drug resistance. Researchers are looking into how ncRNA could also be used to assist in helping with the early detection of cancer. This plays a major role in the prognosis of patients. Identifying cancer at an early stage could pave the way to more efficient and less invasive treatments, possibly even reducing treatment time and the need for hospitalization.
This means the current research into ncRNA would have an impact on more than just patients. It may also assist in reducing the impact of illness on public health systems, which can become critical for ensuring quality of care.
Future Directions
Right now, there are still some limitations in terms of the extent of current research. Ongoing research continues to make breakthroughs in connecting ncRNA network dysfunction to disease pathology.
There’s a strong interest in using ncRNAs as biomarkers for both the diagnosis and prognosis of certain diseases. This is a topic that will continue to see more research, as biomarkers play a critical role in helping medical experts better understand patient health, disease development, and the progression of illnesses. If research continues to identify ways to use ncRNAs as potential biomarkers, it could possibly lead to earlier detection of certain diseases.
When it comes to treating serious illnesses, early detection is a crucial factor that can significantly impact the prognosis. Treatment can be implemented at a stage where the disease might not have become life-threatening, allowing for faster recovery time and potentially a more positive outlook in terms of recovery.
In addition to using ncRNAs as biomarkers, we’re also seeing researchers investigate these molecules as therapeutic targets. This could help provide advancements in medicine and treatments, creating new ways for experts to address specific diseases.
Conclusion
ncRNA has become a new target for scientific studies that focus on better understanding disease pathology. As research in this area continues to evolve, it is becoming increasingly clear that non-coding RNA plays a significant role in disease, and when this network is dysfunctional, it can lead to serious health problems. Even though at an early stage of research, we’ll continue to see improvements in the understanding of ncRNA and how this can be a target to address certain diseases.
References
[1] N. Delihas. Discovery and characteristics of the first non-coding RNA that regulates gene expression micF RNA: A historical perspective. World Journal of Biological Chemistry. 26 Nov 2015. https://pmc.ncbi.nlm.nih.gov/articles/PMC4657122/
[2] M.S. Ilieva. Non-Coding RNAs in Neurological and Neuropsychiatric Disorders: Unraveling the Hidden Players in Disease Pathogenesis. MDPI Cells. 19 Jun 2024. https://pmc.ncbi.nlm.nih.gov/articles/PMC11201512
[3] K. Karaivazoglou, C. Triantos, I. Aggeletopoukou. Non-Coding RNAs in Neurodevelopmental Disorders - From Diagnostic Biomarkers to Therapeutic Targets: A Systematic Review. MDPI. 24 Jul 2025. https://www.mdpi.com/2227-9059/13/8/1808
[4] Cardiovascular diseases (CVDs). World Health Organization. 31 Jul 2025. https://www.who.int/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds)
[5] A. Jusic, Y. Devauz. Noncoding RNAs in Hypertension. AHA|ASA Journals. 29 Jul 2019. https://www.ahajournals.org/doi/10.1161/HYPERTENSIONAHA.119.13412
[6] C. Li, M. Zhou, X. Song, S. Huang, Z. Guo. Regulatory mechanisms of long non-coding RNAs on mitochondrial function in congestive heart failure. KeAi. Mar 2024. https://www.sciencedirect.com/science/article/pii/S246805402300080X
[7] X. Zhou, X. Ao, Z, Jia, et al. Non-coding RNA in cancer drug resistance: Underlying mechanisms and clinical applications. Frontiers in Oncology. 17 Aug 2022. https://pmc.ncbi.nlm.nih.gov/articles/PMC9428469/