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Role of miRNA

Role of miRNA

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dharikasharma1997
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8 views

Role of miRNA

Role of miRNA

Uploaded by

dharikasharma1997
Copyright
© © All Rights Reserved
Available Formats
Download as DOCX, PDF, TXT or read online on Scribd
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Role of mir-138 as a Biomarker for

Early Diagnosis and Prognosis in


Ovarian Cancer.
Abstract :

Points : miR-138 Biogenesis and Function,

Dysregulation of mir-138 in ovarian cancer,

Targets of mir-318 associated with ovarian cancer.,

miRNAs as a Biomarker for Prognosis and Early Diagnosis of Ovarian Cancer

Introduction :
Globally, ovarian cancer ranks fifth in terms of mortality and is the eighth most frequently
occurring cancer among women. Ovarian cancer affects almost 300,000 women and kills
around 152,000 of them annually, with an incidence of 3.4% and a death rate of 4.7%. These
figures demonstrate the severe threat that ovarian cancer poses to women's health and
survival(1). Ovarian cancer symptoms are typically difficult to identify. Most patients with
ovarian cancer are detected in the middle or advanced stages of the disease or have distant
metastases, which results into a poor prognosis. The main causes of ovarian cancer poor
prognosis is recurrence and early tumour cell metastasis. This is because there is a lack of
specific early diagnosis biomarkers(2). Although the 5-year survival rate for individuals with
ovarian cancer has increased dramatically in recent years due to the combination of surgery
and chemotherapy; nonetheless, prognosis remains dismal overall due to treatment resistance,
weak invasiveness, and failure to detect symptoms(3). Over the past half-century, a number
of protein-based biomarkers and physical examination-based diagnostic systems have been
developed. However, they still have conflicting potential as a biomarker. Recent
developments in the molecular study of disease could result in the discovery of promising
Biomarkers with therapeutic and diagnostic value for early cancer diagnosis and better
treatment opportunities(4).

MicroRNAs, also known as endogenous non-coding RNAs, are a family of RNAs with
regulatory activities that are found in eukaryotes(5). The entire proteome is largely
regulated by microRNAs, which are widely distributed across the living kingdom.
Victor Ambros and Gary Ruvkun found the first miRNA gene and its mechanism of
action while studying the Caenorhabditis elegans early development(6). miRNAs are
typically 20 to 25 nucleotides long and can be extracted from biofluids like blood, urine
and saliva(7). miRNAs primarily regulate gene expression in organisms by either
translation-inhibition or degrading target mRNAs(8). Since these circulating miRNAs
are extracted easily and are very stable, which results their packaging into vesicles or
interaction with proteins that protect miRNAs from RNase digestion, these features
could it an ideal choice for biomarkers. miRNAs also act as a regulatory factors
contributing to tumour progression(9).

Many Studies have shown the involvement of miRNA and their role in all stages of cancer,
including carcinogenesis, progression, and metastasis, in the hopes of discovering a new
therapeutic target(10). It has been demonstrated that miRNAs are engaged in several distinct
pathways in cancer cells, including cell cycle(11), differentiation(12), apoptosis and
proliferation(13), and cancer cell metabolism(14). Considering their vital functions in
regulating several metabolic and cellular biological processes, any genetic dysregulation may
result in the development of malignancies(15).

2. Biogenesis of miRNA :

miRNAs can be found within introns or exons of protein-coding genes or located in their
independent regions outside of genes and have their own promoters. Sometimes, several
miRNAs are transcribed together as one long transcript, forming clusters and are grouped as a
family(16). miRNA biogenesis begins with the processing of RNA polymerase II/III
transcripts. The processing can happen either post-transcriptionally or co-
transcriptionally(17). The Mechanism of miRNA biogenesis is a two-step process. RNA
polymerase II makes a long RNA molecule called the primary miRNA transcript (pri-
miRNA) which is cut into a shorter hairpin-shaped molecule called the precursor miRNA
(pre-miRNA) by Drosha. The pre-miRNA is exported from the nucleus to the cytoplasm with
the help of exportin-5 and Ran-GTP. Dicer enzyme cuts the pre-miRNA into a double-
stranded molecule with two short RNA strands (around 22 nucleotides). One strand (mature
miRNA) gets incorporated into a protein complex called RISC (RNA-induced silencing
complex. The other strand, Passenger strand is usually degraded. Different mechanisms exist
to control the expression of individual miRNAs(18). Recent studies suggest that passenger
miRNAs can also bind to RISC and regulate gene expression, although the frequency and
mechanisms are still under investigation(19). This is also known as the Canonical Pathway of
miRNA biogenesis. miRNA production can occur through mechanisms beyond the Drosha-
DGCR8-Dicer pathway which is Drosha/DGCR8-independent, non-canonical pathway.
This pathway bypasses the Drosha-DGCR8 complex (responsible for initial processing in the
nucleus) but still uses Dicer for further processing. The resulting pre-miRNAs resemble
typical Dicer substrates(20).

3. miR-138 Biogenesis and Function:

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