ABSTRACT
[This corrects the article on p. 15632 in vol. 8, PMID: 26884832.].
ABSTRACT
BACKGROUND: It has been reported that deregulation or dysfunction of microRNAs (miRNAs) plays an essential part in the hepatocarcinogenesis. However, the contribution and mechanism of microRNA-30a-5p (miR-30a-5p) in hepatocellular carcinoma (HCC) remains largely unknown. Therefore, our aim was to investigate the clinicopathological role of miR-30a-5p in HCC tissues and explore its potential pathways in this study. METHODS: The expression of miR-30a-5p was measured in 95 HCC and adjacent noncancer tissues by real-time reverse transcription quantitative polymerase chain reaction. The relationship between miR-30a-5p expression levels and clinicopathological parameters was also analyzed. Furthermore, the potential target genes of miR-30a-5p were collected via online prediction and literature searching. Gene ontology and pathway enrichment analyses were used to identify the possible function of miR-30a-5p in HCC. RESULTS: Compared with adjacent noncancer tissues (2.23±0.77), expression level of miR-30a-5p was significantly lower in HCC tissues (1.26±0.66, P<0.001). MiR-30a-5p expression was evidently correlated with tumor nodes, metastasis, tumor-node-metastasis stage, portal vein tumor embolus, vascular invasion, and status of tumor capsule (all P<0.05). A total of 878 genes were finally used for the biological informatics analyses. These prospective target genes were highly enriched in various key pathways, for instance, Ubiquitin-mediated proteolysis, Axon guidance, Neurotrophin signaling pathway, Amyotrophic lateral sclerosis, and ErbB signaling pathway. CONCLUSION: In conclusion, this study clarifies that the downregulation of miRNA-30a-5p might play a vital part in the incidence and progression of HCC via targeting various prospective genes and pathways. Future validation is required to further explore the prospective molecular mechanism of miR-30a-5p in HCC.
ABSTRACT
There has been accumulative evidence that microRNAs (miRNAs) play essential roles in the tumorigenesis and progression of bladder cancer. However, individual studies and small sample size caused discrepant outcomes. Thus, the current study focused on a comprehensive profiling of all differentially expressed miRNAs in a total of 519 bladder cancer tissue samples, based on miRNA microarray data. Altogether, 11 prioritized miRNAs stated by 21 published microarray datasets, including five down-regulated (miR-133a-3p, miR-1-3p, miR-99a-5p, miR-490-5p, and miR-133b) and six up-regulated candidate miRNAs (miR-182-5p, miR-935, miR-518e-3p, miR-573, miR-100-3p, and miR-3171) were analyzed with vote-counting strategy and a Robust Rank Aggregation method. Subsequently, miRNA in silico target prediction and potential pathway enrichment analysis were performed to investigate the prospective molecular mechanism of miRNAs in the tumorigenesis of bladder cancer. We found that most of the relative pathways of the aberrantly expressed miRNAs found in the current study were closely correlated with different biological processes, cellular components, molecular functions, cancer pathogeneses, and some cell signalings, such as Wnt signaling, insulin/IGF, PI3 kinase, and FGF signaling pathways. Hence, a comprehensive overview on the miRNA expression pattern in bladder cancer tissues was gained by the current study. These miRNAs might be involved in the tumorigenesis and deterioration of bladder cancer.
Subject(s)
MicroRNAs/analysis , Urinary Bladder Neoplasms/genetics , Humans , Oligonucleotide Array Sequence Analysis , Urinary Bladder Neoplasms/etiologyABSTRACT
BACKGROUND: MiR-30a-5p has been reported to play vital roles in the carcinogenesis and progression of various malignancies via different molecular mechanisms. However, the role and target genes of miR-30a-5p in hepatocellular carcinoma (HCC) remain still unclear. In silico analysis finds that there are complementary sequences between the 3'-untrasnlated region of astrocyte elevated gene 1 (AEG-1) and miR-30a-5p. Herein, we investigated the biological function of miR-30a-5p, as well as the potential molecular mechanism via targeting AEG-1 in HCC cells. MATERIALS AND METHODS: MiR-30a-5p inhibitor, miR-30a-5p mimic, AEG-1 siRNAs, as well as their negative controls were transfected into HCC cell lines HepG2, SMMC-7221, HepB3 and SNU449. Then, the in vitro influence and mechanism of miR-30a-5p on cell viability, proliferation, caspase-3/7 activity and apoptosis were studied, as assessed by different methods, including spectrophotometry, fluorimetry, fluorescence microscopy of Hoechst 33342/propidium iodide double chromatin staining, western blot and dual luciferase reporter assay, respectively. RESULTS: MiR-30a-5p mimic markedly inhibited cell growth, also induced caspase-3/7 activity and apoptosis in all four HCC cell lines tested. The strongest effect was observed in HepG2 and SMMC-7721 cells. However, this effect was slightly weaker than that of AEG-1 siRNAs. Transfection of miR-30a-5p mimic led to a markedly reduced AEG-1 protein level and further dual luciferase reporter assay confirmed that AEG-1 was one of the target genes of miR-30a-5p in HCC cells. CONCLUSIONS: MiR-30a-5p may play an essential role in the cell growth and apoptosis of HCC cells, partially via targeting AEG-1.
