Cancer Letters

Cancer Letters

Volume 407, 28 October 2017, Pages 123-138
Cancer Letters

Mini-review
MicroRNAs in gynecological cancers: Small molecules with big implications

https://doi.org/10.1016/j.canlet.2017.05.011Get rights and content

Highlights

  • miRNAs affect proliferation, survival, metastasis and chemoresistance of gynecological cancers.

  • miRNAs regulate the tumor microenvironment of gynecological cancers.

  • miRNAs are novel diagnostic and prognostic markers for individual gynecological cancers and their subtypes.

Abstract

Gynecological cancers (GCs) are often diagnosed at advanced stages, limiting the efficacy of available therapeutic options. Thus, there remains an urgent and unmet need for innovative research for the efficient clinical management of GC patients. Research over past several years has revealed the enormous promise of miRNAs. These small non-coding RNAs can aid in the diagnosis, prognosis and therapy of all major GCs, viz., ovarian cancers, cervical cancers and endometrial cancers. Mechanistic details of the miRNAs-mediated regulation of multiple biological functions are under constant investigation, and a number of miRNAs are now believed to influence growth, proliferation, invasion, metastasis, chemoresistance and the relapse of different GCs. Modulation of tumor microenvironment by miRNAs can possibly explain some of their reported biological effects. miRNA signatures have been proposed as biomarkers for the early detection of GCs, even the various subtypes of individual GCs. miRNA signatures are also being pursued as predictors of response to therapies. This review catalogs the knowledge gained from collective studies, so as to assess the progress made so far. It is time to ponder over the knowledge gained, so that more meaningful pre-clinical and translational studies can be designed to better realize the potential that miRNAs have to offer.

Introduction

Gynecological cancers (GCs) are the cancers that originate from, and affect, women's reproductive organs such as cervix, ovary, uterus/endometrium, vagina and vulva. GCs originate in different places within a woman's pelvis, the area between the hip bones and below the stomach. Each GC is unique, with its own signs and symptoms, as well as risk factors. The risk for GCs increases with age. In the United States (US), almost 90,000 women are diagnosed with GCs every year, and more than 28,000 women die from these malignancies [1]. Among the different GCs, ovarian, cervical and endometrial cancers are the most frequent and, thus, considered major women health issues. Although endometrial cancer (EC) is the most common GC among women, ovarian cancer (OC) is the most lethal type [2], and despite scientific advancements, mortality rates of GCs continue to rise [1]. Both early diagnosis and limited treatment options for advanced GCs are contributing factors to their high mortality, emphasizing the need for further advancements in these areas.

Recent years have witnessed growing interest in the field of microRNAs (also referred to as miRNAs/miRs) because of their potential to regulate diverse biological processes [3]. MicroRNAs are small, non-coding RNA molecules, approximately 20–22 nucleotides in length. In general, miRNAs regulate the expression of genes by binding to the 3′-untranslated regions (3′-UTRs) of target messenger-RNAs (mRNAs) with partial or full complementarity, resulting in either translational repression or degradation of target mRNAs [3]. Human genome encodes several thousand miRNAs and the knowledge about their identity and functions is constantly emerging. It is believed that miRNAs regulate the expression of more than one-third of all human genes [4]. In this review article, we discuss deregulation of miRNAs in GCs, their established or putative functions, and clinical and translational relevance. Considering the high incidence and mortality, we will mainly focus on ovarian, cervical and endometrial cancers as the representative GCs.

Section snippets

Dysregulation of miRNAs in gynecologic cancers

Dysregulation of miRNAs in GCs has been reported in multiple studies suggesting their pathobiological importance. Here, we discuss some of these reports on the differential expression of miRNAs in ovarian, cervical and endometrial cancers and highlight their significance in the development and progression of gynecological malignancies (Fig. 1, Table 1).

Biological significance of miRNAs in gynecologic cancers

miRNAs regulate a number of genes with diverse physiological roles. Consequently, the effects of miRNAs are apparent on many biological functions. Some of the better studied biological effects of miRNAs are on cell growth, proliferation, migration, invasion and metastasis. These effects are discussed in next few subsections.

Clinical significance of miRNAs in gynecologic cancers

The discovery of miRNAs and recent knowledge on their role in gynecological cancer pathobiology has created substantial opportunities for translating the miRNA research into clinical settings. Furthermore, data from emerging studies clearly highlight the clinical significance of these miRNAs in the diagnosis and prognosis of gynecologic malignancies. In the sections below, we have described the implication of these miRNAs as potential diagnostic and prognostic biomarkers.

Conclusion and future perspectives

Despite the progress in our understanding of the molecular basis of gynecologic malignancies, no major progress has been made in the improvement of patients' survival. For past several years, microRNAs have established themselves as molecules of interest, with possible implications in diagnosis as well as prognosis of GCs. Some interesting observations have led to promising role of miRNAs in therapy of multiple cancers of gynecological origin. Based on the available and emerging data, miRNAs

Conflict of interest

APS and SS are co-founders and serve on executive management team of Tatva Biosciences LLC, which is involved in the development of tools and models for cancer health disparity research. SKS serves as the Director of Cell Biology and Genetics at Tatva Biosciences LLC.

Acknowledgment

This work is supported by NIH/NCI [CA185490 (to APS) CA204801 (to SS)] and USAMCI. SKS has an SBIR contract funding [HHSN261201600039C] from NIH/NCI.

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