Abstract

Ovarian cancer has the highest mortality rate among gynecological cancers. Early clinical signs are missing and there is an urgent need to establish early diagnosis biomarkers. MicroRNAs are promising biomarkers in this respect. In this paper, we review the most recent advances regarding the alterations of microRNAs in ovarian cancer. We have briefly described the contribution of miRNAs in the mechanisms of ovarian cancer invasion, metastasis, and chemotherapy sensitivity. We have also summarized the alterations underwent by microRNAs in solid ovarian tumors, in animal models for ovarian cancer, and in various ovarian cancer cell lines as compared to previous reviews that were only focused the circulating microRNAs as biomarkers. In this context, we consider that the biomarker screening should not be limited to circulating microRNAs per se, but rather to the simultaneous detection of the same microRNA alteration in solid tumors, in order to understand the differences between the detection of nucleic acids in early vs. late stages of cancer. Moreover, in vitro and in vivo models should also validate these microRNAs, which could be very helpful as preclinical testing platforms for pharmacological and/or molecular genetic approaches targeting microRNAs. The enormous quantity of data produced by preclinical and clinical studies regarding the role of microRNAs that act synergistically in tumorigenesis mechanisms that are associated with ovarian cancer subtypes, should be gathered, integrated, and compared by adequate methods, including molecular clustering. In this respect, molecular clustering analysis should contribute to the discovery of best biomarkers-based microRNAs assays that will enable rapid, efficient, and cost-effective detection of ovarian cancer in early stages. In conclusion, identifying the appropriate microRNAs as clinical biomarkers in ovarian cancer might improve the life quality of patients.

Highlights

  • Ovarian cancer occupies a leading position worldwide, and it is considered to be one of the most lethal cancers

  • CXCL1 activity [110], miR-199a is targeting Hypoxia-inducible factor (HIF)-1α and HIF-2α [111], miR-92α mediates the suppression of peritoneal metastasis by inhibiting α5 integrin [112] and miR-143-3p while using TGF-beta activated kinase 1 (TAK1) signaling [113]; It affects tumorigenesis and chemosensitivity by modulating oxidative stress through the miR-141 and miR-200a regulation at the level of p38α protein [114]; Inhibition of upregulated oncogenic miRs by administration of antisense oligonucleotides and antagomirs or by locked nucleic acid constructs (LNA) [101,115]; The use of therapeutic approaches based on miRNAs in cancer therapy can have multiple benefits

  • This review summarized the role of microRNAs as clinical cancer biomarkers for ovarian cancer

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Summary

Introduction

Ovarian cancer occupies a leading position worldwide, and it is considered to be one of the most lethal cancers. Giannopoulou et al described recent advances on circulating tumor cells and circulating tumor DNA based on liquid biopsy analysis in ovarian cancer and their potential in diagnosis, prognostic and predictive tumor biomarkers [22] It was highlighted the potential of circulating miRNAs in the diagnosis and prognostic of epithelial ovarian carcinoma, with special attention to the subtypes of ovarian cancer, the sample size, the sample subtype (i.e., miRNAs in body fluids), the method of detection, and the survival correlation etc. Our review is focused on the therapeutic potential of miRNAs in ovarian cancer and integrates information regarding circulating miRNAs with their expression changes in ovarian tumors and in ovarian cancer cell lines to offer a new perspective on their quantification in different environments to increase the robustness and reproducibility of using certain miRNAs as reliable biomarkers for the diagnosis/prognosis of this pathology. Exosomal miR-373, miR-200a, miR-200b, and miR-200c were detected in the serum of EOC patients, and there is a correlation between the increased levels of miR-200b and miR-200c and CA125 values, suggesting that these microRNAs may be involved in tumor progression [37]

Ovarian Cancer and miRNA Expression Profiles
Molecular Clustering Analysis in Ovarian Cancer
Findings
Conclusions and Future Perspectives
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