The expression of miR-30a* and miR-30e* is associated with a dualistic model for grading ovarian papillary serious carcinoma

Abstract

Abstract. Histological grade has already been recognized as a very important prognostic factor for ovarian papillary serous carcinoma (OPSC). On the basis of pathogenetic mechanisms, recent findings suggest a dualistic model of OPSC consisting of types I (low-grade) and II (high-grade) cancers. High-grade OPSC is responsible for most ovarian cancer deaths. The goal of our investigation was to identify the differences in key miRNAs and possible regulators through miRNA microarray chip analysis, as well as functional target prediction and clinical outcome between the low and high-grade OPSC patients. The pathogenic basis in differentiation of ovarian cancer subtypes was studied to provide insight into diagnosis and therapy for high-grade cases. Through microarray analysis, we found that miR-30a * and miR-30e * were the top 2 significantly different miRNAs between type I and type II OPSC patients, and both were remarkably downregulated in the latter type. ATF3 and MYC were indicated as potential co-targets of miR-30a * and miR-30e * , and showed a significant upregulation in type II patients. As ATF3 and MYC are often associated with aggressive behavior and poor differentiation, especially in human cancers, these results are in good agreement with our findings and point toward a regulating differentiation function of the miR-30a * and miR-30e * genes. Further analysis using leave-one-out cross predictions and Kaplan-Meier survival analysis strongly suggested that miR-30a * and miR-30e * can be used as biomarkers to tailor histological grade before starting the regimen, and they showed important roles in ovarian cancer differentiation resulting in poorer prognosis. In general, miR-30a * and miR-30e * coupled with expression data that reveal pathogenic regulation to predict histological differentiation, may operate to direct the formation of early detection and therapeutic approaches to individual OPSC patients, especially differentiation therapy to high-grade cases.

Caenorhabditis elegans ALG-1 antimorphic mutations uncover functions for Argonaute in microRNA guide strand selection and passenger strand disposal

“…Although guide strand selection appears to be highly asymmetric for most microRNAs, for a small subset of microRNAs substantial quantities of both 5p and 3p strands can accumulate, and in at least some cases there is evidence for functional roles for both strands (22)(23)(24)(25). It's possible that the relative loading of 5p and 3p strands as the guide could be regulated by upstream signals acting via Argonaute or other components of the miRLC.…”

A comparison of microRNA expression profiles from splenic hemangiosarcoma, splenic nodular hyperplasia, and normal spleens of dogs

“…MicroRNAs in tumor samples have been used to diagnose tumors, provide prognostic information, and aid in targeted treatments in human medicine [18–22]. Many tumor types have been evaluated for differential miRNA expression, including ovarian carcinomas, breast cancer, cervical cancer, non-small cell lung cancer, leukemias, colorectal tumors, squamous cell carcinoma, and hepatocellular carcinoma [21–28]. Use of miRNAs in support of other diagnostic methods is currently in its infancy, with miRNA signatures having been developed in people to distinguish melanoma and metastatic breast cancer from healthy controls and higher risk groups in breast cancer and prostate cancer [29–32].…”

The Versatile Role of microRNA-30a in Human Cancer

“…Furthermore, miR-30a expression decreased in patients with shorter overall survival and disease-free survival time in patients with NSCLC [19] and urothelial carcinoma of bladder [76], consistent with the lower expression of miR-30a in tumor tissues compared to their non-tumor lung tissues. In ovarian papillary serous carcinoma, miR-30a was remarkably negatively related with the grade, and was predicted to be an early detection and therapeutic approach, especially in high-grade cases [74]. Besides, miR-30a was significantly downregulated in the chemoresistant tissues of patients with advanced gastric cancer [77, 78].…”

“…Levels of miR-30a were found to remarkably descend in most of cancer tissues compared with those in adjacent non-tumorous tissues, such as colorectal cancer [67, 68], hepatocellular carcinoma [69, 70], breast cancer [71], renal cell carcinoma [72], chondrosarcoma [73], ovarian papillary serous carcinoma [74], and anaplastic thyroid cancer [75]. Furthermore, miR-30a expression decreased in patients with shorter overall survival and disease-free survival time in patients with NSCLC [19] and urothelial carcinoma of bladder [76], consistent with the lower expression of miR-30a in tumor tissues compared to their non-tumor lung tissues.…”