MicroRNAs in gynecological cancers: Small molecules with big implications

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.

Non-coding RNAs: long non-coding RNAs and microRNAs in endocrine-related cancers

“…Among the miRNAs differentially expressed in EC versus normal endometrial tissue are the increased expression of miR-10b, miR-21, miR-31, miR-182, miR-183, miR-205, miR-222, miR-223, miR-410, miR-429, miR-449a, miR-994, and miR-1228; and downregulation of let-7, miR-34b-5p, miR-34c-3p, miR-34c-5p, miR-99b, miR-101, miR-130a, miR-143, miR-145, miR-184, miR193b, miR-204, miR-340, miR-372, miR-429, miR-449a, miR-490, and miR-495 (reviewed in (Srivastava, et al 2017)). In serum samples from women with EC, increased levels of miR-186, miR-222, and miR-223 were identified compared with controls (Montagnana, et al 2017).…”

“…Targets of upregulated miRs in EC include the tumor suppressor PTEN that is downregulated by overexpressed miR-21, miR-130a, miR-205, miR-222, and miR-429 (Srivastava et al 2017). …”

“…Although much studied, there are currently no miRNA signatures in use for early detection and screening of gynecological cancers (Srivastava et al 2017).…”

MicroRNA‐367‐3p overexpression represses the proliferation and invasion of cervical cancer cells through downregulation of SPAG5‐mediated Wnt/β‐catenin signalling

“…Dysregulated miRNAs can regulate the malignant behaviours of cancer cells, including proliferation, cell cycle, migration and invasion, through targeting and regulating various oncogenes or tumour suppressors . To date, a growing body of evidence has demonstrated that various miRNAs participate in the development and progression of cervical cancer and can be utilized as biomarkers for the diagnosis and prognosis of the disease, as well as therapeutic targets . Therefore, better understanding of the miRNA‐regulated molecular mechanisms occurring throughout cervical cancer progression will help researchers to develop novel miRNA‐based anticancer therapy for cervical cancer.…”

Acidic extracellular environment affects miRNA expression in tumors in vitro and in vivo

“…5 Many studies have analyzed the expression patterns of miR-NAs in different tumor entities and correlated them with the prognosis of the individual patient. [4][5][6][7] Functionally miRNAs can modulate the proliferation of tumor cells, 8 the migration and the metastatic potential, 9 the process of epithelialmesenchymal transition 8,9 or the sensitivity of tumor cells to chemotherapy. 10 MiRNAs also regulate the adequate development of tissues and organs.…”