Exosomal lncRNA NEAT1 from cancer-associated fibroblasts facilitates endometrial cancer progression via miR-26a/b-5p-mediated STAT3/YKL-40 signaling pathway.

Cancer-associated fibroblasts cells (CAFs) confer a rapid growth and metastasis ability of endometrial cancer (EC) via exosomes-mediated cellular communication. Long non-coding RNA nuclear enriched abundant transcript 1 (lncRNA NEAT1) drives the malignant phenotypes of EC cells. However, the role of exosomal NEAT1 from CAFs in EC progression remains ambiguous, which needs to be investigated. In our study, NEAT1 and YKL-40 were up-regulated, while miR-26a/b-5p was down-regulated in EC tissues. Moreover, NEAT1 expression was increased in CAF-exosomes compared with that in NF-exosomes. In addition, the exosomal NEAT1 derived from CAFs could transfer to EC cells and promote YKL-40 expression. Further exploration showed that exosomal NEAT1 enhanced YKL-40 expression via regulating miR-26a/b-5p-STAT3 axis in EC cells. More importantly, exosomal NEAT1 accelerated in vivo tumor growth via miR-26a/b-5p-STAT3-YKL-40 axis. Taken together, our study reveals that exosomal NEAT1 from CAFs contributes to EC progression via miR-26a/b-5p-mediated STAT3/YKL-40 pathway, which indicates the therapeutic potential of exosomal NEAT1 for treating EC.

Upregulated miR­203a­3p and its potential molecular mechanism in breast cancer: A study based on bioinformatics analyses and a comprehensive meta­analysis.

Breast cancer (BC) has been identified as the leading malignancy in women worldwide. However, the potential molecular mechanism of microRNA (miR)­203a­3p in BC remains to be elucidated. The present study evaluated the expression of miR­203a­3p in BC and adjacent normal tissue in several publically available datasets. The distinguishability of precursor miR­203a and miR­203a­3p in BC tissue and adjacent breast tissue was assessed using receiver operating characteristic (ROC) and summarized ROC (sROC) approaches. In addition, gene ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes pathway analysis and protein­protein interaction analysis were performed to determine the potential molecular mechanism of miR­203a­3p in BC. It was identified that the expression of precursor miR­203a was markedly upregulated in 1,077 BC tissue samples compared to 104 adjacent breast tissue samples from The Cancer Genome Atlas. Additionally, an increasing trend in miR­203a­3p expression was observed in 756 BC tissue samples compared with 76 adjacent breast tissue samples from the University of California Santa Cruz Xena project. In addition, a comprehensive meta­analysis suggested that the expression of miR­203a­3p was markedly increased in 2,444 BC tissue samples compared with 559 adjacent breast tissue samples. The area under the curve of the ROC and sROC revealed that miR­203a­3p expression was able to distinguish between BC tissue and adjacent breast tissue. However, miR­203a­3p exhibited no prognostic value in BC. The results of GO enrichment demonstrated that the miR­203a target genes were associated with 'plasma membrane integrity', 'cell surface receptor linked signal and transduction' and '3',5'­cyclic nucleotide phosphodiesterase activity'. 'Purine metabolism' was identified as the pathway with the most enrichment of miR­203a­3p target genes in BC. The present study also identified insulin­like growth factor receptor (IGF1) as a hub gene associated with miR­203a in BC. In summary, miR­203a­3p may enhance the development and oncogenesis of BC, and IGF1 was defined as a hub gene of miR­203a­3p in BC.

A comprehensive insight into the clinicopathologic significance of miR-144-3p in hepatocellular carcinoma.

BACKGROUND: Studies which focused on the character of miR-144-3p in hepatocellular carcinoma (HCC) are limited. This study aimed to explore the expression, clinical significance and the potential targets of miR-144-3p in HCC. METHODS: The Cancer Genome Atlas (TCGA) and a cohort of 95 cases of HCC were applied to investigate aberrant miR-144-3p expression in HCC. A meta-analysis was performed to accumulate data on miR-144-3p expression in HCC based on TCGA, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Gene Expression Omnibus (GEO). Additionally, the potential regulatory mechanisms of miR-144-3p in HCC were explored by bioinformatics. RESULTS: MiR-144-3p expression was downregulated distinctly in HCC compared to para-HCC tissue both in TCGA data (8.9139±1.5986 vs 10.7721±0.9156, P<0.001) and in our qRT-PCR validation (1.3208±0.7594 vs 2.6200±0.9263, P<0.001). The meta-analysis based on TCGA, qRT-PCR and GEO data confirmed a consistent result (standard mean difference =-0.854, 95% CI: -1.224 to -0.484, P<0.001). The receiver operating characteristic curve of miR-144-3p gained a significant diagnostic value both in TCGA data (area under the curve [AUC] =0.852, 95% CI: 0.810 to 0.894, P<0.001) and in qRT-PCR validation (AUC =0.867, 95% CI: 0.817 to 0.916, P<0.001), especially in alpha-fetoprotein-negative HCC patients (AUC =0.900, 95% CI: 0.839 to 0.960, P<0.001). Furthermore, we identified 119 potential targets of miR-144-3p in HCC by bioinformatics. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that several significant biologic functions and pathways correlated with the pathogenesis of HCC, including the p53 signaling pathway. CONCLUSION: MiR-144-3p may function as a cancer suppressor microRNA, which is essential for HCC progression through the regulation of various signaling pathways. Thus, interactions with miR-144-3p may provide a novel treatment strategy for HCC in the future.