The Role of miRNAs in the Regulation of Endometrial Cancer Invasiveness and Metastasis-A Systematic Review.

Klaudia Klicka,Alicja Klinke,Paweł K Włodarski,Tomasz M Grzywa,Aleksandra Mielniczuk

doi:10.3390/cancers13143393

Abstract

Simple SummaryEndometrial cancer (EC) is one of the most frequent cancers with increasing annual death rates. Therefore, it is of great clinical importance to understand the mechanisms of endometrial cancer invasiveness and metastasis. MiRNAs are small single-stranded RNAs that regulate gene expression. They were discovered to play a role in all steps of cancer development. This study aimed at conducting a systematic review of the role of miRNAs in endometrial cancer invasiveness and metastasis. The collected data demonstrate that miRNAs regulate EC invasiveness and metastasis by different targets. MiRNAs seem to be potential candidates for diagnostic and prognostic biomarkers, as well as possible therapeutic targets.Endometrial cancer (EC) is the most common genital cancer in women with increasing death rates. MiRNAs are short non-coding RNAs that regulate gene expression on the post-transcriptional levels. Multiple studies demonstrated a fundamental role of miRNAs in the regulation of carcinogenesis. This systematic review is a comprehensive overview of the role of miRNAs in the regulation of cancer cell invasiveness and metastasis in EC. The literature was searched for studies investigating the role of miRNAs in the regulation of invasiveness and metastasis in EC. We explored PubMed, Embase, and Scopus using the following keywords: miRNA, metastasis, invasiveness, endometrial cancer. Data were collected from 163 articles that described the expression and role of 106 miRNAs in the regulation of EC invasiveness and metastasis out of which 63 were tumor suppressor miRNAs, and 38 were oncomiRNAs. Five miRNAs had a discordant role in different studies. Moreover, we identified 66 miRNAs whose expression in tumor tissue or concentration in serum correlated with at least one clinical parameter. These findings suggest a crucial role of miRNAs in the regulation of EC invasiveness and metastasis and present them as potential prognostic factors for patients with EC.

Highlights

Endometrial cancer (EC) accounts for the most frequent cancers with growing incidence rates [1,2]
The search strategy provided a total of 270 records in the PubMed database, 245 in the Embase, 121 in the Scopus database, and three records identified through other sources
Data were collected from 163 articles demonstrating the role of miRNA in the regulation of EC invasiveness or metastasis

Summary

Introduction

Endometrial cancer (EC) accounts for the most frequent cancers with growing incidence rates [1,2]. The outcome depends on the progression of the disease and applied treatment [3,4]. That makes effective management of EC risk factors, early diagnosis, and effective therapy strategies of EC the clinically important challenges. There are two most common EC staging classifications, TNM and The International Federation of Gynecology and Obstetrics (FIGO) that differentiate endometrial cancer tumors according to the depth of invasion and presence of metastases (Figure 1) [5]. There is a FIGO grading based on the level of glandular differentiation. A higher grade is associated with a non-glandular, non-squamous growth [6]

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