MicroRNAs and their role in gynecological tumors

Abstract

There have been only few events in the history of molecular biology that could be compared to the discovery of microRNAs and their role in cell physiology and pathology. MicroRNAs are small, single-stranded, noncoding RNAs composed of 19-25 nucleotides (∼22 nt), which have been proven to regulate gene expression at the posttranscriptional level. The regulatory function of microRNAs was demonstrated in normal and diseased conditions. In particular, it has been linked to cell cycle regulation, cell proliferation and differentiation, inflammatory response, and apoptosis. Altered expression profiles of microRNA have been observed in many pathologies, including diabetes, rheumatoid arthritis, and several cancers. To date, more than 700 human microRNAs have been identified and in silico-based analyses estimate at least 500 more to be identified. The purpose of this review is to present the current perspective on microRNAs structure and biogenesis as well as their contribution to the etiopathogenesis of gynecological tumors. We discuss results of the recent publications that indicate possibilities of microRNAs use as novel markers for tumors screening, early diagnosis, and treatment monitoring. The possible utilization of microRNAs as prognostic factors and specific therapy targets is also reviewed.

Microvesicles as Potential Ovarian Cancer Biomarkers

“…Furthermore, some miRNAs are consistently and significantly overexpressed in ovarian cancer, including miRNAs belonging to the miR-200 family (i.e., miR-200a, miR-200c, and miR-200b), whereas miRNAs of the let-7 family, miR-140, miR-145, and miR-125b1 are consistently downregulated in ovarian cancer. Altered expression has also been reported for other miRNAs, such as miR-21, miR-99a, miR-125b, and miR-199a [78, 93, 95] (Table 1). Moreover, a correlation between miRNA features and chemoresponse was also reported in other cancers, including leukemia, colorectal adenocarcinoma, and breast, pancreatic, and lung cancers, which indicates the potential use of miRNAs for diagnosis and predicting patient survival rates and risk of recurrence [78, 96–101].…”

“…Altered expression has also been reported for other miRNAs, such as miR-21, miR-99a, miR-125b, and miR-199a [78, 93, 95] (Table 1). Moreover, a correlation between miRNA features and chemoresponse was also reported in other cancers, including leukemia, colorectal adenocarcinoma, and breast, pancreatic, and lung cancers, which indicates the potential use of miRNAs for diagnosis and predicting patient survival rates and risk of recurrence [78, 96–101]. It is interesting to note that miRNAs can be detected in the bloodstream; however, for stable expression, miRNAs must be protected from RNases, which are abundant in the blood and are able to degrade approximately 99% of RNA species within 15 min [102].…”

“…Ovarian cancer is the most lethal gynecologic malignancy and is characterized by poor prognosis with an overall 5-year survival rate of approximately 50%. If the cancer is diagnosed while confined to the ovary, the 5-year survival rate could become 90%, but this occurs only in a small percentage of patients (approximately 20%) [78, 79]. Ovarian cancer can be identified at the following four stages: stage I, the cancer is limited to one or both ovaries; stage II, the cancer is present in one or both ovaries as well as in pelvic extensions or implants; stage III, peritoneal implants are present outside of the pelvis or are limited to the pelvis with an extension to the small bowel or omentum, and there may also be metastasis on the liver surface; stage IV, distant metastases to the parenchymal compartment of the liver or outside of the peritoneal cavity are present [80].…”

MicroRNA in Cervical Cancer: OncomiRs and Tumor Suppressor miRs in Diagnosis and Treatment

“…Poly A-binding protein (PABP) binds to the 3′ poly A tail of the mRNA to attract eIF4G to mRNAs, and thus translation is initiated by synergistic action of the mRNA cap structure and poly A tail. The RNA-induced silencing complex (RISC) containing a miRNA binds the 3′-UTR in mRNAs and induces formation of the CCR4-CAF1-NOT complex, a poly A tail-truncating enzyme, resulting in truncation of the downstream poly A tail, reduced binding of translation initiation factors, and repression of translation [4]. …”

Changes in the Expression of Serum MiR-887-5p in Patients With Endometrial Cancer

“…Since then, numerous studies have shown that miRNAs regulate cell differentiation, cell cycle, inflammation, and apoptosis. 6 Genes encoding miRNAs are first transcribed by RNA polymerase II to produce precursor miRNAs containing 60 to 100 nucleotides. 7 These precursor miRNAs are modified by RNA polymerase III and are converted into stem loop-shaped precursor miRNAs containing 60 nucleotides by endonuclease Drosha and cofactor DGCR8.…”