A Key mRNA-miRNA-lncRNA Competing Endogenous RNA Triple Sub-network Linked to Diagnosis and Prognosis of Hepatocellular Carcinoma

MiR-195 suppresses tumor growth and is associated with better survival outcomes in several malignancies including non-small cell lung cancer (NSCLC). Our previous study showed high miR-195 plasma levels associated with favorable overall survival of non-smoking women with lung adenocarcinoma. To further elucidate role of miR-195 in NSCLC, we conducted in vitro experiment as well as clinical studies in a cohort of 299 NSCLC samples. We demonstrated that miR-195 expression was lower in tumor tissues and was associated with poor survival outcome. Overexpression of miR-195 suppressed tumor cell growth, migration and invasion. We discovered that CHEK1 was a direct target of miR-195, which decreased CHEK1 expression in lung cancer cells. High expression of CHEK1 in lung tumors was associated with poor overall survival. Our results suggest that miR-195 suppresses NSCLC and predicts lung cancer prognosis.

Background Hepatocellular carcinoma (HCC) is third leading cause of cancer-related death globally. Evidence suggest that long non-coding RNAs (lncRNAs) have emerged as key regulators of tumorigenesis and metastasis in HCC. In this study, we investigated the functional significance of SNHG12 and explored whether SNHG12 can directly interact with miR-199a/b-5p in the progression of HCC. Methods We determined the expression level of SNHG12 in HCC tissues with quantitative real-time PCR and then studied its clinical significance. The binding site between SNHG12 and miR-199a/b-5p was confirmed using dual luciferase assay and RNA immunoprecipitation (RIP) assay. SNHG12 was silenced through the siRNA transfection to determine whether SNHG12-siRNA is able to affect cell proliferation, invasion and metastasis. Results SNHG12 was significantly higher in the HCC tissues than that in the adjacent normal tissues. There were direct interactions between miR-199a/b-5p and the binding site of SNHG12. SNHG12 functioned as an endogenous sponge for miR-199a/b-5p to regulate the expression of MLK3 and affect the NF-κB pathway. Conclusion SNHG12 may serve as a valuable biomarker and a potential therapeutic target for HCC.

Background Hepatitis B virus (HBV) is one of the major risk factors of hepatocellular carcinoma (HCC). Increasing evidence indicates that microRNA (miRNA)–mRNA axis is involved in HCC. However, a comprehensive miRNA–mRNA regulatory network in HBV-related HCC is still absent. This study aims to identify potential miRNA–mRNA regulatory pathways contributing to pathogenesis of HBV-related HCC. Methods Microarray GSE69580 was downloaded from Gene Expression Omnibus (GEO) database. GEO2R and ‘R-limma’ were used to conduct differential expression analysis. The common miRNAs appeared in the two analytic sets were screened as potential differentially expressed miRNAs (DE-miRNAs). The prognostic roles of screened DE-miRNAs in HCC were further evaluated using Kaplan–Meier plotter database. Target genes of DE-miRNAs were predicted by miRNet. Then, protein–protein interaction (PPI) networks were established for these targets via the STRING database, after which hub genes in the networks were identified by Cytoscape. Functional annotation and pathway enrichment analyses for the target genes were performed through DAVID database. Three enriched pathways related to HBV-related HCC were selected for further analysis and potential target genes commonly appeared in all three pathways were screened. Cytoscape was employed to construct miRNA-hub gene network. The expression and correlation of potential miRNAs and targets were further detected in clinical HBV-related HCC samples by qRT-PCR. Results 7 upregulated and 9 downregulated DE-miRNAs were accessed. 5 of 7 upregulated DE-miRNAs and 5 of 7 downregulated DE-miRNAs indicated significant prognostic roles in HCC. 2312 and 1175 target genes were predicted for the upregulated and downregulated DE-miRNAs, respectively. TP53 was identified as the hub gene in the PPI networks. Pathway enrichment analysis suggested that these predicted targets were linked to hepatitis B, pathways in cancer, microRNAs in cancer and viral carcinogenesis. Further analysis of these pathways screened 20 and 16 target genes for upregulated and downregulated DE-miRNAs, respectively. By detecting the expression of 36 target genes, six candidate target genes were identified. Finally, a potential miRNA–mRNA regulatory network was established based on the results of qRT-PCR and expression correlation analysis. Conclusions In the study, potential miRNA–mRNA regulatory pathways were identified, exploring the underlying pathogenesis and effective therapy strategy of HBV-related HCC. Electronic supplementary material The online version of this article (10.1186/s12967-018-1761-7) contains supplementary material, which is available to authorized users.