Crucial Role of microRNAs as New Targets for Amelogenesis Disorders
Detection
Authors: Masunova Nadezhda , Tereschenko Maria , Alexandrov Georgy , Spirina Liudmila , Tarasenko Natalia 
Published: November 2023

Introduction:
Amelogenesis imperfecta (AI) refers to a heterogeneous group of conditions
with multiple factors which contribute to the hypomineralisation of enamel. Preventive measures
are necessary to predict this pathology. Prospects for preventive medicine are closely related
to the search for new informative methods for diagnosing a human disease. MicroRNAs are prominent
for the non-invasive diagnostic platform.

The Aim of the Study:
The aim of the review is to review the heterogeneous factors involved in
amelogenesis and to select the microRNA panel associated with the AI type.

Methods:
We used DIANA Tools (algorithms, databases and software) for interpreting and archiving
data in a systematic framework ranging from the analysis of expression regulation from deep sequencing
data to the annotation of miRNA regulatory elements and targets (https://dianalab.
e-ce.uth.gr/). In our study, based on a gene panel associated with the AI types, twenty-four miRNAs
were identified for the hypoplastic type (supplement), thirty-five for hypocalcified and forty--
nine for hypomaturation AI. The selection strategy included the microRNA search with multiple
targets using the AI type's gene panel.

Results:
Key proteins, calcium-dependent and genetic factors were analysed to reveal their role in
amelogenesis. The role of extracellular non-coding RNA sequences with multiple regulatory functions
seems to be the most attractive. We chose the list of microRNAs associated with the AI
genes. We found four microRNAs (hsa-miR-27a-3p, hsa-miR-375, hsa-miR-16-5p and hsamiR-
146a-5p) for the gene panel, associated with the hypoplastic type of AI; five microRNAs (hsa-
miR-29c-3p, hsa-miR-124-3p, hsa-miR-1343-3p, hsa-miR-335-5p, and hsa-miR-16-5p - for
hypocalcified type of AI, and seven ones (hsa-miR-124-3p, hsa-miR-147a, hsa-miR-16-5p, hsamiR-
429, hsa-let-7b-5p, hsa-miR-146a-5p, hsa-miR-335-5p) - for hypomaturation. It was revealed
that hsa-miR-16-5p is included in three panels specific for both hypoplastic, hypocalcified, and hypomaturation
types. Hsa-miR-146a-5p is associated with hypoplastic and hypomaturation type of
AI, which is associated with the peculiarities of the inflammatory response immune response. In
turn, hsa-miR-335-5p associated with hypocalcified and hypomaturation type of AI.

Conclusion:
Liquid biopsy approaches are a promising way to reduce the economic cost of treatment
for these patients in modern healthcare. Unique data exist about the role of microRNA in regulating
amelogenesis. The list of microRNAs that are associated with AI genes and classified by
AI types has been uncovered. The target gene analysis showed the variety of functions of selected
microRNAs, which explains the multiple heterogeneous mechanisms in amelogenesis.
Predisposition to mineralisation problems is a programmed event. Many factors determine the manifestation
of this problem. Additionally, it is necessary to remember the variable nature of the
changes, which reduces the prediction accuracy. Therefore, models based on liquid biopsy and microRNAs
make it possible to take into account these factors and their influence on the mineralisation.
The found data needs further investigation.