Circulating RNA in diseases and diagnosis
BS 7th (2021-2025)
Submitted By:
Laiba Rashid
Roll no. 40 (E )
Submitted to:
Sir Z.Q. Samra.
Date:
29th Jan 2025.
Circulating RNA in diseases and diagnosis
Circulating RNA refers to RNA molecules that are present in body fluids such as blood, plasma,
serum, urine, or saliva. These RNA molecules are released by cells into the bloodstream or other
body fluids either through normal physiological processes or as a result of disease conditions.
Circulating RNA has attracted significant interest in the fields of disease diagnosis, monitoring,
and prognosis because it can serve as a non-invasive biomarker for a variety of diseases.
Types of Circulating RNA:
1. mRNA (messenger RNA):
Carries genetic information from DNA to the ribosome for protein synthesis. The presence
and levels of certain mRNAs can indicate the activity of specific genes related to diseases,
including cancer.
2. miRNA (microRNA):
Small non-coding RNA molecules that regulate gene expression by binding to messenger
RNAs and preventing their translation. They are often stable in circulation and can be used to
diagnose and monitor diseases like cancer, cardiovascular disease, and neurological
disorders.
3. lncRNA (long non-coding RNA):
These are longer RNA molecules that do not encode proteins but are involved in regulating
gene expression. Altered expression of lncRNAs is associated with diseases, including
cancer.
4. Viral RNA:
In viral infections (e.g., HIV, Hepatitis, SARS-CoV-2), viral RNA can be detected in
circulation, allowing for the diagnosis and monitoring of the disease.
Circulating RNA can be used as a biomarker to help diagnose, monitor, and predict the course of
diseases.
miRNA (micro-RNA)
miRNAs can be used as biomarkers for diseases like nonalcoholic fatty liver disease and
chronic heart disease. Certain miRNAs, including miR-122 and miR-21, are involved in liver
function and fibrosis. These miRNAs can serve as biomarkers for liver disease, including
hepatitis, cirrhosis, and liver cancer. It plays essential roles in cardiovascular development,
function, and response to injury. Several miRNAs have been identified as biomarkers for
myocardial infarction (heart attack), heart failure, and other heart diseases.
lncRNA (long non-coding RNA):
lncRNAs play a role in fundamental biological processes like cell differentiation and
transcription regulation.
ctRNA (circulating tumor RNA):
ctRNA can be used as a biomarker to provide information about tumors. It refers to RNA
molecules that are released into the bloodstream from tumor cells. Like circulating tumor DNA
(ctDNA), ctRNA is an important biomarker that is increasingly being studied for its potential in
cancer diagnosis, prognosis, and monitoring treatment response.
The Value of Circulating Circular RNA in Cancer Diagnosis:
Liquid biopsy can eliminate the tumor heterogeneity effect by determining the genomic profile
of cancer patients, assist with a systemic and comprehensive representation of disease, help with
early cancer detection (even before radiological and imaging tests detect the presence of tumors),
aid in evaluating therapeutic reaction, detect minimal residual disease, and test for cancer cells’
drug resistance. Besides blood, several other body fluids such as urine, saliva, pleural effusions,
and cerebrospinal fluid (CSF) as well as stool can be used to reveal information about the tumor.
Biofluid sampling and analysis provide an accurate account of the molecular traits of primary
tumors and distant metastases. Most liquid biopsy analyses have displayed their clinical utility in
human cancers. The first important milestone in this field was reached in 2016 with the Food and
Drug Administration (FDA) approval of the first companion diagnostic test for lung cancer based
on the circulating tumor DNA (ctDNA) content of a liquid biopsy.[1]
The Value of Circulating Circular RNA in Cardiovascular Diseases:
Cardiovascular diseases are the leading cause of death globally and are associated with
increasing financial expenditure. With the availability of next-generation sequencing
technologies since the early 2000s, non-coding RNAs such as microRNAs, long non-coding
RNAs and circular RNAs have been assessed as potential therapeutic targets for numerous
diseases, including cardiovascular diseases. In this Review, we summarize current approaches
employed to screen for novel coding and non-coding RNA candidates with diagnostic and
therapeutic potential in cardiovascular disease, including next-generation sequencing, functional
high-throughput RNA screening and single-cell sequencing technologies. Furthermore, we
highlight viral-based delivery tools that have been widely used to evaluate the therapeutic utility
of both coding and non-coding RNAs in the context of cardiovascular disease. Finally, we
discuss the potential of using oligonucleotide-based molecular products such as modified RNA,
small interfering RNA and RNA mimics/inhibitors for the treatment of cardiovascular diseases.
Given that many non-coding RNAs have not yet been functionally annotated, the number of
potential RNA diagnostic and therapeutic targets for cardiovascular diseases will continue to
expand for years to come.[2]
Circulating RNA Molecules as Biomarkers in Liver Disease:
In the context of an ever-increasing need for noninvasive molecular markers in medicine,
circulating RNA molecules have become appealing biomarker candidates in liver disease.
However, many aspects related to their origin and biological significance, remain to be clarified.
Moreover, a long-acknowledged heterogeneity of technical methods employed in the assessment
and interpretation of circulating RNA levels imposes a more comprehensive standardization and
harmonization of biological assays.
The aim is to highlight recent advances in the study of circulating RNA molecules as biomarkers
in liver pathology, and to provide a short overview on the biological properties of these
molecules and the analytical challenges in their assessment.[3]
Circulating RNAs as new biomarkers for detecting in cerebrovascular
diseases:
MicroRNAs (miRNAs) are composed of a group of endogenous and noncoding small RNAs
which control expression of complementary target mRNAs. The extended functions of miRNAs
enhance the complexity of gene-regulatory processes in cardiovascular and cerebrovascular
diseases. Indeed, recent studies have shown that miRNAs are closely related to myocardial
infarction, heart failure, atrial fibrillation, cardiomyopathy, hypertension, angiogenesis, coronary
artery disease, dyslipidaemia, stroke, and so forth. These findings suggest a new therapeutic
pointcut for cardiovascular and cerebrovascular diseases and show the extensive therapeutic
potential of miRNA regulation. Moreover, it has been shown that circulating extracellular
miRNAs are stable in bodily fluids, which indicates circulating miRNAs as potential and
emerging biomarkers for noninvasive diagnosis. This review highlights the most recent findings
indicative of circulating miRNAs as potential clinical biomarkers for diagnosis of cardiovascular
and cerebrovascular diseases.[4]
Circulating RNAs as new biomarkers for detecting in neurological disorders:
Circulating RNA holds considerable promise in the field of neurological disorders, offering a
non-invasive, potentially early diagnostic tool and a way to monitor disease progression and
response to treatments. Although challenges like RNA stability, variability, and the blood-brain
barrier remain, ongoing research continues to reveal how circulating RNA can aid in the
understanding and management of neurological diseases. As these methods become more
refined, circulating RNA may play a central role in the future of personalized medicine for
neurological disorders.
Circulating RNA in infectious diseases:
Circulating RNA has the potential to revolutionize the diagnosis and management of infectious
diseases by offering a non-invasive, early, and dynamic means of tracking both pathogen and
host responses. From viral infections like HIV and COVID-19 to bacterial infections like sepsis
and tuberculosis, circulating RNA provides a window into the molecular processes that underlie
infection, offering insights that can guide diagnosis, treatment, and monitoring. While challenges
related to RNA stability, interpretation, and variability remain, ongoing research into circulating
RNA continues to hold promise for improving infectious disease care.
Limitations and Future Directions
Circulating miRNAs or miRNA combinations can be used as potential biomarkers for diagnosis
and prognosis of cardiovascular and cerebrovascular diseases. However there still exist several
problems. Firstly, the samples of the studies aimed to identify circulating miRNAs as biomarkers
of cardiovascular and cerebrovascular diseases are relatively small. The conclusions should be
validated in independent and large cohort studies. Secondly, the expression profile of circulating
miRNAs may change depending on the disease state, which makes it difficult to determine
appropriate endogenous controls. Thirdly, RNA isolation from blood and subsequent
quantification by real-time PCR consume time. So it is necessary to find a better method to
detect circulating miRNAs, which makes it available in clinic. With development of high-
throughput platforms including multiplex PCR and microarrays, the next-generation-sequencing
technology has quickly emerged as the preferred platform for studying circulating miRNAs. The
next-generation-sequencing technology has the ability to pool and sequence multiple samples in
one lane of a sequencer, which makes it possible to construct comprehensive expression profiles
for every assessed sample and lower the costs significantly. In the future, circulating miRNAs
may be extensively used in clinical diagnosis. Moreover, it has potential to detect and predict the
therapeutic effect of cardiovascular and cerebrovascular diseases.
References:
1. Zhang, Y., et al., The value of circulating circular RNA in cancer diagnosis, monitoring, prognosis,
and guiding treatment. Frontiers in oncology, 2021. 11: p. 736546.
2. Lu, D. and T. Thum, RNA-based diagnostic and therapeutic strategies for cardiovascular disease.
Nature Reviews Cardiology, 2019. 16(11): p. 661-674.
3. Enache, L.S., et al., Circulating RNA molecules as biomarkers in liver disease. International
journal of molecular sciences, 2014. 15(10): p. 17644-17666.
4. Li, M. and J. Zhang, Circulating MicroRNAs: potential and emerging biomarkers for diagnosis of
cardiovascular and cerebrovascular diseases. BioMed Research International, 2015. 2015(1): p.
730535.