Int J Biol Med Res.

2025; 16(1): 7974-7979

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Review Article

MicroRNAs in Personalized Medicine: Targeted Therapeutic Interventions and Their Emerging Role as Non-
Invasive Biomarkers in Cancer Biology
Kehinde Adedapo Olajide*¹, Ekundina Victor Olukayode², Moronkeji Akinpelu³, Oloruntobi Olutayo Oluwaseun⁴

¹Department of Histopathology and Cytopathology,Faculty of Medical Laboratory Sciences, Achievers University, Owo, Ondo State, Nigeria.

²Department of Medical Laboratory Science, College of Medicine and Health Sciences, Afe Babalola University, Ado-Ekiti, Ekiti State, Nigeria.

³Department of Medical Laboratory Science, Faculty of Allied Health Sciences, University of Medical Sciences, Ondo City, Ondo State, Nigeria.

⁴Department of Medical Microbiology and Parasitology, Faculty of Medical Laboratory Sciences, Achievers University, Owo, Ondo State, Nigeria.

ARTICLEINFO ABSTRACT

Keywords: Micro Ribonucleic acids (microRNAs or miRNAs) have gained attention in the research community in the
microRNA, last decade due to their roles in genetics and cancer biology. Initially, when compared to other nucleic acids
Cancer biology, their roles were considered insignificant.An extensive study conducted recently on miRNAs has provided a
oncology, wealth of knowledge regarding the background functions of microRNAs, most importantly, their role in the
cancer, pathophysiology of diseases such as cancer, gene expression or silencing, protein-coding gene modulation,
targeted therapeutics, cell differentiation, proliferation, and death.Therehas been significant progress made in the identification of
genes, the origin of miRNAs which has given researchers and scientists in Nigeria, Africa and the world at large,
diagnostic markers, the privy to focus on their diagnostic potential usage in both clinical fields for investigating the pathological
precision medicine. mechanism of diseases and also in the field of research, thus, creating the opportunity to use miRNAs as
a predictive non-invasive biomarker in different disease conditions such as Prostrate cancer, Cervical
cancer, Esophageal squamous cell carcinoma, Ovarian Cancer, Breast Cancer, Lung cancer, etc., and thus a
potential target in therapeutic inventions for this disease conditions in developing parts of the world, in like
countries like Nigeria, where the prevalence of these diseases are increasing.Nonetheless, issues such as the
standardisation of miRNA quantity, the normal range of miRNA value within the plasma, and the unification
of diagnostic techniques for miRNA quantification continue to be debated among various scientific schools of
thought; however, its diagnostic importance continues to outweigh the challenges of this new era diagnostic
markers.

© Copyright 2023 BioMedSciDirect Publications IJBMR -ISSN: 0976:6685.

Introduction Deoxyribonucleic acid molecules (dsDNA) that are double-stranded

unwind into two single strands. These strands are often transcribed into
The disintegration of double-stranded RNAs (dsRNAs) yields bi- RNA molecules, which are then translated into protein molecules, which
product fragments, including microRNAs (miRNAs) and other products are used to make amino acids. Usually, single-stranded transcripts,
like siRNAs and shRNAs. miRNAs are naturally occurring, non-coding ribonucleic acid molecules (RNAs) can couple to generate double-
RNA molecules with between 20 and 24 nucleotide base pairs. They stranded RNA molecules (dsRNAs), which resemble hairpins[4], which
work with target messenger ribonucleic acids (mRNA) to either limit serve as the mother strand and starting template for the synthesis of
translation or destroy the molecule [1].A brief mention of Francis Crick’s microRNA molecules.
1957 “Central Dogma Biology” [2], Robert Griffith’s 1928 experiment,
Avery’s 1944 experiment, and Meselson & Stahl’s 1958 experiment would be Figure 1: The fundamental principle of life (DNA to RNA to Protein
incomplete discussing microRNAs without acknowledging these important Replication)[5].
contributions to the discovery of deoxyribonucleic acid (DNA).

Corresponding author:

Kehinde Adedapo Olajide

Department of Histopathology and Cytopathology,
Faculty of Medical Laboratory Sciences,
Achievers University, Owo, Ondo State, Nigeria
Email: [email protected]
OrcidID: 0009-0008-8166-2183

© Copyright 2023 BioMedSciDirect Publications IJBMR -ISSN: 0976:6685.

 Kehinde Adedapo Olajide et al, Int J Biol Med Res. 2025; 16(1): 7974-7979
7975

Methodology is present in physiological fluids such as breast milk, urine, saliva,

blood, and seminal fluid [8]. This movement, known as plasma miRNAs,
This is a systematic review study that used about 52 journals was has been the subject of much study over the past 20 years [6]. It can
used for this review study. They included journals indexed on Google also arise from tissue injury, apoptosis, and necrosis, as well as from
Scholar, EPUB, CrossRef, Scopus, DOAJ, Embase, Global Health, MEDLINE, an active passage in microvesicles, exosomes, or binding to a protein.
PubMed Central, and SCImago.
The phenomenon of a “message in a bottle” type of intercellular
The Process of MicroRNA Biosynthesis. communication has been discovered in some research studies, where
the assimilation of exosomes by neighbouring cells is demonstrated in
Double-stranded RNA is used in the complex, multi-step manufacturing vitro. This has now been researched as a means of getting information
of miRNA molecules, which takes place in both the cytoplasm and through miRNAs on several pathological mechanisms and the state
the nucleus [6]. The double stranding of RNA molecules is peculiar. A of diseases within the human body, and this is the most promising
terminal looped Hairpin-like double-stranded RNA molecule, known role of miRNAs, as a “biomarker” [1,6]. Because microRNAs facilitate
as the Pri-microRNA, is created when RNA polymerase II transcribes intercellular communication through exosomes, they play a significant
DNA molecules into RNA molecules. These RNA molecules are typically role as biomarkers in the diagnosis and prognosis of cancer.
single-stranded and have a long nucleotide base sequence. Because the
bases have complements between them, the nucleotide bases have a high Some significant Micro RNAs as Biomarkers in Cancer Biology
affinity to bind together by hydrogen bond. Pri-microRNAs are about
Cancer is a leading cause of mortality worldwide, making it an
100–120 nucleotides long.
important public health problem and research priority.A breakthrough
The Pri-miRNA is broken down into shorter Pre-miRNA by the action in the scientific study of microRNAs, particularly as a biomarker, is
of the enzymes Drosha and DGCR8 (Di George syndrome critical region that they are stable, have a wide pH range, can resist the activity of
8).A transmembrane protein molecule known as Exportin-5 then endonuclease enzymes, can be stored for long periods, and are readily
moves the pre-miRNA molecule from the nucleus into the cytoplasm. found in plasma, resulting in a non-invasive method for the early
It attaches to the pre-miRNA molecule and positions it for cleavage by detection of various types of cancer and the significant role they play in
a double-stranded RNA-specific endonuclease Dicer enzyme, known cancerogenesis.
as RNase III enzyme. Typically, this process prepares the Pre-miRNA
for activation by cleaving off the hairpin region of the Pre-miRNA, 1. miRNAs in Breast Cancer (BC).
producing a 5’ monophosphate region and a two-nucleotide overhang
at 3’ dsRNA known as miRNA:miRNA*duplex, which is attached to the Studies have suggested that microRNAs miR-10b, miR-196a, and miR-
RNA interference complex known as RISC (RNA interference silencing 4417 play an important role in the pathology of breast cancer. miR-10b
complex) [7]. A slicer enzyme and an Argonaut protein makeup RISC. is up-regulated in BC and overexpressed in metastatic BC. A high level
of miR-10b correlates with breast cancer progression, inducing cell
The Argonaut protein, an RNase H type possessing a Paz domain and a invasion and metastasis, suspected to increase oncogene RhoC.Similarly,
PIWI region, is the exclusive target of the miRNAs.The dsmiRNA:miRNA* miR-196a is up-regulated in BC and plays an oncogenic function by
duplex is unravelled by the argonaut into two single miRNA strands: a altering apoptosis and angiogenesis; high levels of miR-196a are seen in
guide strand and a passenger strand. Only the guide strand, which makes advanced BC. miR-4417, on the other hand, is found to be down-regulated
up the active mature miRNA molecule, remains when the passenger in BC, indicating the progression of the disease. Furthermore, it has been
strand is released [8]. To form a nuclear hybrid structure (Nucleation), revealed that ncRNA-regulated reprogramming of glucose metabolism in
these mature miRNA strands and the RISC complex bind to the target breast cancer through glycolysis, lactate production, glycogen synthesis
messenger RNA strand (mRNA). This is done by first identifying a and catabolism, and the tricarboxylic acid cycle [6,13].
complementary 2-4 nucleotide on the target mRNA and then forming a
double-stranded messenger RNA (ds mRNA), which would be cleaved 2. miRNAs in Ovarian Cancer (OVC)
and broken/degraded by the RNase H.
miR-200 cluster, miR-506, let-7 cluster, miR-183, and miR-22 all play
This process plays a crucial role in gene silencing and has been applied important roles in the diagnosis and prognosis of OVC. In addition, the
to the diagnosis and prognosis of conditions such as cancer [1], diabetic miR-200 cluster is up-regulated in OVC, and a low level of it is associated
nephropathy [9], and neurological illnesses. [10], key biomarkers for with cell invasion and metastasis and is used to predict a poor treatment
the detection of specific cancers, such as ovarian cancer [10]. According outcome and possible recurrence. It also acts as an angiogenesis
to Condrat et al. [6], miRNAs are also helpful in the diagnosis and
inhibitor by targeting IL-8 and CXCL-1 produced by tumour cells.
prognosis of neurodegenerative illnesses, spinal cord injuries, epilepsy,
They inhibit transcriptional inhibitors of E-cadherin, ZEB1, and ZEB2,
and Alzheimer’s disease. They also have a significant impact on endemic
promoting E-cadherin expression and the transformation into epithelial
tropical parasitic infections, including those caused by Plasmodium
cells of mesenchymal cells (EMT). Additionally, they are linked to TGF-β,
falciparum, Toxoplasma gondii, and Cryptosporidium parvum [7,12].
affecting cell invasion and migration, both of which are crucial in cancer
progression [6,14].
Figure 2: Modified microRNAs’ biological production[8]
This cluster can influence tumour development and metastasis,
making them potential biomarkers for OVC prognosis. miR-506 is a
modulator of E-cadherin and inhibits cell invasion, migration, and
EMT through another one of its transcriptional suppressors, known as
SNAI2 [15]. When expressed in ovarian cancer, miR-506 was reported
to be associated with a good prognosis. Its contribution to OVC is seen
in its pathway’s modulation, such that it is involved in proliferation,
metastasis, and apoptosis. It affects cellular processes essential for cancer
progression by targeting genes in the PI3K/Akt/mTOR pathway [16].

The let-7 cluster was found to have a suppressing effect on tumour

growth and cell invasion [16], and it influences cell proliferation,
differentiation, and apoptosis by Ras and HMGA2 pathways regulation
MicroRNAs in Disease pathophysiological and Role in diagnosis
[18]. Similarly, miR-183 and miR-22 were found in low metastatic OVC
and Prognosis
having a metastasis-inhibiting role. The former impacts cell proliferation
and migration by its action on the PI3K/Akt/mTOR and TGF- β signalling
Through their roles in mRNA degradation, transcription and translation
pathways [19] while the latter affects tumour growth and prognosis in
regulation, and intercellular signalling, miRNAs are essential for the
OVC with its involvement in the regulation of genes that are responsible
regulation of genes in the human body. The majority of microRNAs
for cell cycle control and apoptosis [20].
are located inside cells, but a sizable fraction also leaves the cell and
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3. miRNAs in Cervical Cancer (CC) target a single gene, miRNAs can regulate the expression of numerous
genes that are involved in the same biological pathway or disease process
In cervical cancer, miRNA-20a, miRNA-21, miRNA-203, miRNA-205, [30]. This multifaceted approach allows for a more comprehensive and
miRNA-485-5, miR-7, miR-10a, miR135b, and miR-149 were found to effective treatment strategy, particularly for complex diseases with
be over expressed. miR-21a plays a crucial role in CC as reported by multiple gene abnormalities.
Farzami [21] who noted a significant increase in miR-21 expression
in cancerous samples. It was found to stimulate inflammation and The development of synthetic miRNAs and anti-miRs has further
proliferation and inhibit apoptosis through angiogenesis, cell invasion, accelerated the progress of miRNA-based therapies. Synthetic miRNAs
and transduction of the NF-kB pathway [22]. Also, miR-944 was reported are designed to mimic the function of endogenous miRNAs, while
to be significantly up-regulated in CC. miR-138, miR-148b, miR-195, and anti-miRs are designed to inhibit the activity of specific miRNAs. Both
miR-214 were reported to be down-regulated and are suspected to be approaches can be used to restore or modulate gene expression patterns
tumour suppressors [23,24,25]. miR-138 is being found to stimulate in disease cells [34]. Synthetic miRNAs can be delivered to target cells
apoptosis and prevent cell migrations; similarly, miR-664 in HeLa cells using various delivery systems, such as nanoparticles, liposomes, or viral
is found to allow a higher sensitivity of cervical cancer cells to cisplatin vectors. These delivery systems protect the miRNAs from degradation
and lowered cell migration in the course of the disease [26]. and facilitate their uptake by target cells, ensuring efficient and specific
delivery to the desired tissues or organs[34].
4. miRNAs in Prostrate cancer
Nanoparticles, in particular, have revolutionized the field of miRNA
According to Moya et al. [27], there is dysregulation of several delivery. These tiny particles can be engineered to encapsulate
microRNAs in prostate cancer patients as compared to healthy and protect miRNAs, enhancing their stability and bioavailability.
individuals. These microRNAs include miR-4289, miR-326, miR-152-3p, Additionally, nanoparticles can be surface-modified with ligands that
and miR-98-5p. However, the mechanism by which these miRNAs impact specifically recognize and bind to receptors on target cells, enabling
cell proliferation and metastasis in prostate cancer remains unclear. precise targeting and delivery [36]. This targeted approach minimizes
off-target effects and improves the therapeutic efficiency of miRNA-
5. miRNAs in oesophagal squamous cell carcinoma based therapies.

This cancer is regarded to be one of the most aggressive malignancies; Possible Perspective Role of miRNAs in Medicine
it is diagnosed using an invasive biopsy method and the CK-19 and
Cyfra21-1 markers. Certain microRNAs from the miR-17-92 cluster were It has been reported that developing nations haveutilised miRNAs
significantly expressed in ESCC [28], particularly MiR-19a, which was in medical diagnostics to improve disease diagnosis and prognosis. In
found to be more sensitive than the previously used tumour markers, the case of prostate cancer, a study conducted in South Africa identified
CK-19 and Cyfra21-1, as well as more specific, as MiR-19a was found to and quantified EV miRNAs in the blood plasma of patients with low and
be significantly reduced after cancer removal [29]. high Gleason score prostate cancer. The researchers found that the ratio
between two miRNAs (miR-194-5p/miR-16-5p) was significantly higher
6. miRNAs in Lung Cancer in prostate cancer patients compared to those with benign prostatic
hyperplasia (BPH). This ratio can serve as a non-invasive marker for
Lung cancer is a frequent disease that kills millions of people evaluating the aggressiveness of prostate cancer in the South African
worldwide each year. Szelenberger et al. [1] found that plasma miR-145, population [37].In the context of breast cancer, microRNAs have also
miR-20a, miR-21, miR-223, miR-324-3p, and miR-19b were up-regulated shown promise as non-invasive biomarkers for diagnosis [38]. However,
in the plasma of lung cancer patients, whereas miR-1285, miR-25, and it is important to consider genetic and environmental factors that may
miR-183 were down-regulated; however, miR-19b was dysregulated [1]. influence the accuracy of these biomarkers.
They also found that miR-145 targeted PDK1 on the mTOR signalling
pathway, preventing lung cancer cell invasion and migration. MiR-210 A study by Uyisenga et al. [39] conducted in Rwanda evaluated the
has also been connected to regulating tumour cells’ hypoxia response effectiveness of a diagnostic circulating microRNA signature for breast
in lung cancer. cancer in different populations with findings showing that the circulating
microRNA signatures identified were not accurate enough for use as a
Micro RNAs in targeted gene therapy diagnostic test in both populations. However, accurate signatures were
found for each specific population separately further highlighting the
MicroRNAs have emerged as promising targets for gene therapy importance of considering population-specific factors when utilizing
due to their ability to fine-tune gene expression and control various microRNAs for diagnostic purposes [39].These studies demonstrate how
cellular processes [30].By targeting specific miRNAs, researchers aim Africa, including Nigeria, is actively involved in harnessing the potential
to manipulate gene expression patterns and restore normal cellular of microRNAs for medical diagnostics. By identifying and quantifying
function, making miRNAs a potential therapeutic strategy for various specific miRNAs, researchers can develop non-invasive markers to aid
diseases, including cancer [31]. MiRNAs have shown promise in cancer in the diagnosis and prognosis of diseases such as prostate cancer and
treatment by targeting oncogenes or tumour suppressor genes. For breast cancer.
instance, miR-34a mimics have been developed to mimic the tumour-
suppressing function of this miRNA, which is often down-regulated in However, further research is needed to validate and refine these
various cancers [32]. miRNA biomarkers to ensure their accuracy and applicability in
different populations [37,39].Nigeria, as one of the leading countries in
These mimics have been tested in preclinical models to inhibit tumour Africa, has been making strides in exploring the potential of miRNAs in
growth.MiRNAs have also been investigated as potential therapeutic medical diagnostics. Nigeria, like many African nations, faces significant
targets for cardiovascular diseases, neurological disorders, and viral challenges with infectious diseases such as malaria, HIV/AIDS, and
infections [33]. MiR-208, for example, plays a role in cardiac hypertrophy. tuberculosis [40]. Researchers in Nigeria have been investigating miRNA
In preclinical studies, inhibiting miR-208 has shown potential in profiles associated with these diseases. For instance, studies have
reducing heart failure progression. In Alzheimer’s disease, miR-29 has examined miRNA expression patterns in malaria-infected individuals,
been implicated in the regulation of amyloid precursor protein (APP) aiming to identify potential biomarkers for early detection and
processing.Modulating this miRNA might offer a therapeutic strategy monitoring of treatment response [41]. Efforts have also been directed
for altering APP metabolism. In viral infections such as hepatitis C, MiR- towards understanding miRNA involvement in cancers prevalent in the
122, abundantly expressed in the liver, is necessary for hepatitis C virus region, like breast and cervical cancers.
(HCV) replication [32].
Research endeavours have aimed to identify specific miRNA
Antisense oligonucleotides against miR-122 have been investigated as signatures that could aid in the early diagnosis and prognosis of these
a potential therapy to inhibit HCV replication.One of the key advantages cancers [42]. Such studies are vital considering the high incidence and
of miRNA-based gene therapy is its ability to target multiple genes mortality rates associated with these cancers in Nigeria. Furthermore,
simultaneously [34]. Unlike traditional gene therapy approaches that given the increasing burden ofnon-communicable diseases in Nigeria,
 Kehinde Adedapo Olajide et al, Int J Biol Med Res. 2025; 16(1): 7974-7979
7977

including cardiovascular diseases and diabetes, investigations into Conclusion

miRNA biomarkers for early detection and monitoring of these
conditions have gained attention [43]. Research efforts have explored Although the need to bring this technique to a unified, globally
the association between certain miRNAs and disease progression, accepted standard and determine a normal range is urgent, miRNAs
paving the way for potential diagnostic applications. are the newest diagnostic tools for optimizing investigations, diagnosis,
and treatment. MicroRNA profiling for the diagnosis and prognosis
Nigerian researchers and institutions have collaborated domestically of diseases is quickly becoming a major cornerstone, especially in
and internationally to further explore miRNA-based diagnostics. Efforts Western medicine, and has great “unmined” potential that should be
have included collaborative studies, workshops, and capacity-building researched and explored for non-invasive methods of early detection
programs aimed at enhancing expertise in miRNA research and its and management of diseases such as cancer.Medical researchers and
application in diagnostics within the country and while progress has practitioners, particularly in African nations such as Nigeria, should
been made in exploring miRNA diagnostics in Nigeria, challenges such endeavour to incorporate it as a diagnosis approach for cancer, therapy,
as limited infrastructure, funding constraints, and the need for extensive and management, as this would help to reduce the growing occurrence
clinical validation persist. Collaborations between Nigerian researchers, of these disorders.
healthcare professionals, and global partners are essential to overcome
these challenges and translate miRNA research into practical and List of abbreviations
accessible diagnostic tools for the Nigerian population.
miRNAs : Micro Ribonucleic acids
Challengesand issues related to MicroRNA as a therapeutic RNAs : Ribonucleic acids
dsDNA : Deoxyribonucleic acid
Although multiple subtypes of miR-19 have been identified in many DGCR8 : Di George syndrome critical region 8
cancer types, the use of miRNAs for cancer diagnosis and prognosis RISC : RNA interference silencing complex
has shown to be rather particular for the cancer type in question. The OVC : Ovarian Cancer
standardization of the amount of miRNA to be utilized for the assay HCV : hepatitis C virus
and the lack of knowledge and clinical acceptance of the typical range
of miRNA values that should be observed in the plasma are two key Acknowledgements
problems with the usage of miRNAs.
Not applicable.
To test patient plasma samples, several researchers [44, 45, 46] had
to develop their panel of miRNAs using PCR techniques; a thorough Authors’ contributions
investigation is still required in this field of miRNA science to ensure
proper standardization. As a result, researchers continue to employ KA and OOconceptualized the study. All authors collected and analysed
data and drafted the manuscript. KA and OO reviewed and edited the
a variety of methodologies to investigate plasma miRNA levels, with
manuscript. All authors approved the final manuscript.
microarrays being one of the most popular methods due to their
reputation as the most suitable for handling huge amounts of data.
Funding
Additionally, quantitative real-time PCR, or QRT-PCR, is employed. This research did not receive any grant from funding agencies in the
It is said to be the most accurate, sensitive, and specific diagnostic test public, commercial,or not-for-profit sectors.
for identifying a small number of miRNAs due to its high repeatability,
sensitivity, and precision. Another technique for monitoring miRNA Availability of data and materials
gene expression in clinical practice is next-generation sequencing (NGS),
although it is very costly and time-consuming. According to Mestdagh’s They included journals indexed on Google Scholar, EPUB, CrossRef,
research [47], there were variations in the sensitivity, repeatability, Scopus, DOAJ, Embase, Global Health, MEDLINE, PubMed Central, and
specificity, and accuracy of all the methodologies employed for miRNA SCImago.
investigation.
Declarations
The traditional techniques include northern blotting, quantitative
polymerase chain reaction (qPCR), and microarray analysis; these are Ethics approval and consent to participate
all noted for their limitations, emphasizing the exploration of newer
techniques for the highly sensitive detection of miRNAs [48]. Of all these Not applicable.
techniques, Quantitative Real-Time PCR (QRT-PCR) showed the best
levels of sensitivity, specificity, and detection rate of the miRNAs [49]. Consent for publication

Despite the enormous potential of miRNA therapeutics, there are still Not applicable.
several challenges that need to be overcome. One major hurdle is the
efficient delivery of miRNAs to target cells [50]. The delivery systems Competing interests
must be able to navigate biological barriers, such as the extracellular
matrix and cell membranes, to reach the desired intracellular Authors declare no competing interest
compartments. Additionally, the stability and release kinetics of miRNAs
within the delivery systems need to be optimized to ensure sustained References
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