Prognostic Significance of miR-205 in Endometrial Cancer

Abstract

PurposemicroRNAs have emerged as key regulators of gene expression, and their altered expression has been associated with tumorigenesis and tumor progression. Thus, microRNAs have potential as both cancer biomarkers and/or potential novel therapeutic targets. Although accumulating evidence suggests the role of aberrant microRNA expression in endometrial carcinogenesis, there are still limited data available about the prognostic significance of microRNAs in endometrial cancer. The goal of this study is to investigate the prognostic value of selected key microRNAs in endometrial cancer by the analysis of archival formalin-fixed paraffin-embedded tissues.Experimental DesignTotal RNAs were extracted from 48 paired normal and endometrial tumor specimens using Trizol based approach. The expression of miR-26a, let-7g, miR-21, miR-181b, miR-200c, miR-192, miR-215, miR-200c, and miR-205 were quantified by real time qRT-PCR expression analysis. Targets of the differentially expressed miRNAs were quantified using immunohistochemistry. Statistical analysis was performed by GraphPad Prism 5.0.ResultsThe expression levels of miR-200c (P<0.0001) and miR-205 (P<0.0001) were significantly increased in endometrial tumors compared to normal tissues. Kaplan-Meier survival analysis revealed that high levels of miR-205 expression were associated with poor patient overall survival (hazard ratio, 0.377; Logrank test, P = 0.028). Furthermore, decreased expression of a miR-205 target PTEN was detected in endometrial cancer tissues compared to normal tissues.ConclusionmiR-205 holds a unique potential as a prognostic biomarker in endometrial cancer.

MicroRNA-205 Directly Regulates the Tumor Suppressor, Interleukin-24, in Human KB Oral Cancer Cells

“…2B). This shows that miR-205 was down-regulated significantly in the KB oral cancer cells as well as in other cancer cells, such as melanoma Xu et al, 2012), bladder cancer , prostate carcinoma (Boll et al, 2012), endometrial cancer (Karaayvaz et al, 2012) and breast cancer (Adachi et al, 2011). These results suggest that over-expressed miR-205 would increase the level of apoptotic cell death in KB cells.…”

How to Explain the Contradiction of microRNA 200c Expression and Survival in Solid Tumors?: a Meta-analysis

“…Like this article, other three studies estimated the prognostic value of miRNA 200c expression in tumor tissue (Yu et al, 2010;Marchini et al, 2011;Karaayvaz et al, 2012). Among these studies, two studies reported HR and its 95% CI (Marchini et al, 2011;Toiyama et al, 2013) and the rest ones were processed by Matthew Sydes and Jayne Tierney's method to acquire survival data (Tierney et al, 2007;Marchini et al, 2011;Karaayvaz et al, 2012). HRs (high vs low) were pooled by fixedeffects model ( Figure 2B, …”

Insights into the Diverse Roles of miR-205 in Human Cancers

“…A number of recent studies have investigated the expression profiles of miRNAs in endometrial cancer Cohn et al, 2010;Ratner et al, 2010;Snowdon et al, 2011). Several studies reported elevated expression level of miR-205 in different types of endometrial cancer compared to normal endometrial tissues and plasmas (Boren et al, 2008;Hiroki et al, 2010;Karaayvaz et al, 2012). Its aberrant expression is proved to be associated with advanced stage in endometrial cancer (Chung et al, 2009), and with overall ratio of survival such that patients with higher levels of miR-205 tend to have a worse survival phenotype (Karaayvaz et al, 2012).…”

“…Several studies reported elevated expression level of miR-205 in different types of endometrial cancer compared to normal endometrial tissues and plasmas (Boren et al, 2008;Hiroki et al, 2010;Karaayvaz et al, 2012). Its aberrant expression is proved to be associated with advanced stage in endometrial cancer (Chung et al, 2009), and with overall ratio of survival such that patients with higher levels of miR-205 tend to have a worse survival phenotype (Karaayvaz et al, 2012). miR-205 is further confirmed to negatively regulate cellular proliferation, migration and invasion properties (Su et al, 2013), with this regard, a number of target mRNAs are investigated to be associated with miR-205 in endometrial cancer.…”

“…Previous studies have identified PTEN to be mutated in 34-55% of endometrial cancers (Kong et al, 1997;Risinger et al, 1997;Tashiro et al, 1997), and acts as an important tumor suppressor in endometrial cell lines (Greene et al, 2010). Some cohort studies revealed that high levels of miR-205 are significantly inversely correlated with the PTEN expression levels, and associated with poor survival of patients, implying the notion that expression levels of miR-205 may consider as a putative negative prognostic biomarker in endometrial cancer (Karaayvaz et al, 2012;Qu et al, 2012). Su et al (Su et al, 2013) identified estrogen-related receptor γ (ESRRG) as a direct target of miR 205 in human endometrial endometrioid carcinoma (EEC).…”