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Review
. 2021 Jul 6;13(14):3393.
doi: 10.3390/cancers13143393.

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

Klaudia Klicka  1   2 , Tomasz M Grzywa  1   2   3 , Alicja Klinke  1 , Aleksandra Mielniczuk  1 , Paweł K Włodarski  1
Affiliations
Review

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

Klaudia Klicka et al. Cancers (Basel). .

Abstract

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.

Keywords: biomarker; endometrial cancer; invasiveness; metastasis; miRNAs; migration.

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Conflict of interest statement

The authors declare no conflict of interest of the study. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Federation of Gynecology and Obstetrics (FIGO) staging and histological grading of endometrial cancer. Figure was created using Biorender.com.
Figure 2
Figure 2
PRISMA flow-chart diagram of study selection. n = number of articles. Figure was created using Biorender.com.
Figure 3
Figure 3
miRNAs regulating cell invasiveness and cell migration in vitro as well as tumor growth, and metastasis in vivo. Figure was created using Biorender.com.
Figure 4
Figure 4
Direct targets of invasion-regulating miRNAs. cAMP—Cyclic Adenosine Monophosphate, EMT—epithelial–mesenchymal transition, ECM—extracellular matrix, JAK-STAT—Janus Kinase/Signal Transducers and Activators of Transcription, PI3K/AKT—Phosphatidylinositol 3-Kinase/Protein Kinase B. Figure was created using Biorender.com.
Figure 5
Figure 5
miRNAs as diagnostic biomarkers and therapeutics. miRNAs are promising biomarkers that can be analyzed either from tumor tissue (1) or from blood obtained from EC patients (2). miRNAs may support EC diagnosis and indicate primary and adjuvant treatment. Moreover, their expression is an important prognostic factor. miRNA-based therapies that include tumor suppressor miRNAs and anti-oncomiRNAs are currently tested in preclinical and clinical trials (3). EVs—extracellular vesicles, FFPE—formalin-fixed, paraffin-embedded. Figure was created using Biorender.com.
See this image and copyright information in PMC

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