Circulating miR-3613-5p but not miR-125b-5p, miR-199a-3p, and miR-451a are biomarkers of endometriosis.

OBJECTIVE: This study aimed to assess the utility of circulating miR-125b-5p, miR-199a-3p, miR-451a, and miR-3613-5p as biomarkers of endometriosis. STUDY DESIGN: Patients with stage III or IV of endometriosis according to the revised American Society of Reproductive Medicine (rASRM) staging classification, as well as control women, were recruited. We created a prospective study conducted on a group of 48 patients (n = 25 controls, n = 24 endometriosis) who had laparoscopic surgery. Blood samples were taken and plasma miRNA levels were measured by quantitative real-time polymerase chain reaction (RT-qPCR) and assessed with AUC and ROC curves. RESULTS: MiR-451a and miR-3613-5p were significantly decreased in the plasma of endometriosis patients. miR-451a had a receiver-operating characteristic (ROC) area under the curve 0.8283 and miR-3613-5p had a ROC area under the curve 0.7617. The concentration of circulating miR-125b-5p and miR-199-3p did not differ between endometriosis patients and controls. Plasma miRNA levels did not change with BMI, smoking status, fertility problems, or menstrual pain according to the VAS scale (p > 0.05). CONCLUSION: Circulating miR-451a and miR-3613-5p levels significantly differed between endometriosis and controls. However, the levels of miR-451a were discordant with previous studies. Therefore, miR-3613-5p may have better potential as the endometriosis biomarker. Circulating miR-125b-5p and miR-199a-3p cannot be used as reliable markers of endometriosis.

KMO in the promotion of tumor development and progression in hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is one of the most common cancers and an important medical problem with poor prognosis. The role of messenger RNA (mRNA) has been broadly researched in the progression of different human cancers. Microarray analysis has demonstrated that kynurenine 3-monooxygenase (KMO) expression is lower in HCC, but the mechanism of KMO in regulating the development of HCC remains unknown. Methods: Through comprehensive bioinformatics analysis of GSE101728 and GSE88839, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, protein-protein interaction (PPI) network analysis, gene expression, and overall survival (OS) analysis, KMO was selected as the candidate molecular marker in HCC. The expression of KMO at the protein and RNA level was evaluated by Western blotting (WB) and quantitative real-time polymerase chain reaction (qRT-PCR). Furthermore, the cell proliferation, migration, invasion, and apoptosis, and the protein levels of epithelial-mesenchymal transition (EMT) markers were examined with Cell Counting Kit 8 (CCK-8) assays, Transwell assay, flow cytometry, and WB. Results: Through comprehensive bioinformatics analysis, we found that the low expression of KMO in HCC is not conducive to a good prognosis of HCC. Then, through in vitro cell experiments, we found that low expression of KMO promoted HCC proliferation, invasion, metastasis, EMT, and cell apoptosis. Additionally, hsa-miR-3613-5p was found to be highly expressed in HCC cells and could negatively regulate the expression of KMO. Moreover, hsa-miR-3613-5p was found to be the target microRNA (miRNA) of KMO according to qRT-PCR verification. Conclusions: KMO plays an important role in the early diagnosis, prognosis, occurrence, and development of liver cancer, and may target miR-3613-5p to function. This represents a novel insight into understanding the molecular mechanisms of HCC.

miR-3613-5p enhances the metastasis of pancreatic cancer by targeting CDK6.

Pancreatic cancer (PC) is a leading cause of cancer mortality and is expected to continue increasing incidence. Abnormally expressed microRNAs have been demonstrated tightly correlated with the development and progression of PC. However, the molecular mechanisms remain largely unknown. In this study through combing both the TCGA database and our two verification PC cohorts, we found the consistent reduction of miR-3613-5p in PC tumors, which significantly correlated with reduced cumulative survival rate among PC patients. PC patients with higher lymph node metastasis rate show reduced miR-3613-5p expression. Through further mechanistic investigation, we demonstrate that miR-3613-5p down-regulated CDK6 in repressing the metastasis capacity of PC cells in vitro and in vivo. Elevated CDK6 were also found in PC samples, which also correlate with poor prognosis. Thus, our study found a novel tumor repressor miR-3613-5p in PC progression.