Crucial Role of microRNAs as New Targets for Amelogenesis Disorders Detection.

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.

Transcription factors Brn-3α and TRIM16 in cancers, association with hormone reception.

Sex hormones, regulating normal physiological processes of most tissues and organs, are considered to be one of the key factors in the development of hormone-dependent cancer and formation of the hormone-resistant tumor phenotype. Recently, the importance of the system for control of hormone receptors expression mediated by nuclear peptides became evident. This system is involved in the regulation of normal physiological processes, in the pathogenesis of many diseases as well as oncogenesis. In the review, we discuss the relationships of the two regulatory peptides - Brn-3α, TRIM16 with hormone receptors. The transcription factor Brn-3α is able to affect the transcription activity of androgen and estrogen receptors. It is observed the participation of TRIM16 protein in the pathogenesis of hormone-dependent tumors due to its "anti-estrogenic effect". Additionally, they are involved in the key intracellular processes, such as proliferation, cell differentiation, and programmed death - apoptosis. Thus, Brn-3α and TRIM16 are associated with cancer development and progression. By understanding these alterations, we can identify potential markers and novel biochemical therapeutic targets. It makes clear the association between classical hormone-dependent tumors and less sensitive ones with the modification in the level of hormone receptors.

[Targeting of the AKT/m-TOR Pathway: Biomarkers of Resistance to Cancer Therapy--
AKT/m-TOR Pathway and Resistance to Cancer Therapy].

Resistance to cancer therapy continues to be a major limitation for the successful treatment of cancer. There are many published studies on therapy resistance in breast and prostate cancers; however, there are currently no data on molecular markers associated with resistance. The conflicting data were reported regarding the AKT/m-TOR signaling pathway components as markers predicting resistance. The AKT/m-TOR signaling pathway is involved in the development of many human cancers; its activation is related to cell proliferation, angiogenesis, apoptosis, as well as to therapy resistance. Molecular alterations in the AKT/m-TOR signaling pathway provide a platform to identify universal markers associated with the development of resistance to cancer therapy.