Dataset Information

Clinical significance of miR-1180-3p in hepatocellular carcinoma: a study based on bioinformatics analysis and RT-qPCR validation.

ABSTRACT: miRNAs play an indispensable role in human carcinogenesis. Dysregulated miR-1180-3p has been observed in several types of cancer, including hepatocellular carcinoma (HCC). This study intends to correlate the expression level of miR-1180-3p with clinical features and overall survival in HCC patients. The expression and clinical significance of miR-1180-3p, selected from GEO and TCGA databases, were verified using an RT-qPCR method. The target genes of miR-1180-3p were obtained using 3 miRNA target gene prediction databases, and their functions were analyzed using the online tool WebGestalt. miR-1180-3p expression was significantly upregulated in 88 HCC tissues compared with non-tumor liver tissues (0.004?±?0.009 vs. 0.002?±?0.002, t?=?-?2.099, P?=?0.038). Additionally, we found that the expression levels of miR-1180-3p were significantly correlated with tumor number (?2?=?9.157, P?=?0.006) and MVI (?2?=?11.354, P?=?0.003). Based on Kaplan-Meier analysis, patients with high miR-1180 expression had a shorter overall survival than those with low miR-1180-3p expression (P?=?0.002). Furthermore, multivariate Cox analyses indicated that miR-1180-3p expression was an independent prognostic factor for overall survival (HR?=?13.36, 95% CI 1.16, 153.69, P?=?0.038). In addition, a total of 733 target genes of miR-1180-3p were found from three prediction databases. The GO analyses demonstrated that the target genes were closely related to the proliferation and malignancy of tumors. The KEGG analysis showed that target genes were enriched in several key cancer-related signaling pathways, including the Pathways in cancer, the Ras signaling pathway, and the MAPK signaling pathway. In conclusion, we demonstrate that miR-1180-3p is upregulated in HCC and is associated with a poor prognosis. Thus, miR-1180-3p might be useful as a prognostic marker for HCC.

SUBMITTER: Zhou Z

PROVIDER: S-EPMC7360737 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Clinical significance of miR-1180-3p in hepatocellular carcinoma: a study based on bioinformatics analysis and RT-qPCR validation.

Zhou Zihan Z Zhou Xianguo X Jiang Yanji Y Qiu Moqin M Liang Xiumei X Lin Qiuling Q Guo Qian Q Nong Cunli C Huo Rongrui R Chen Qian Q Liu Haizhou H Liu Yingchun Y Zhu Shaoliang S Wang Mengyun M Yu Hongping H

Scientific reports 20200714 1

miRNAs play an indispensable role in human carcinogenesis. Dysregulated miR-1180-3p has been observed in several types of cancer, including hepatocellular carcinoma (HCC). This study intends to correlate the expression level of miR-1180-3p with clinical features and overall survival in HCC patients. The expression and clinical significance of miR-1180-3p, selected from GEO and TCGA databases, were verified using an RT-qPCR method. The target genes of miR-1180-3p were obtained using 3 miRNA targe ...[more]

PMID: 32665670

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Project description:Mounting evidence has shown that miR-23b-3p, which is associated with cell proliferation, invasion, and apoptosis, acts as a biomarker for diagnosis and outcomes in numerous cancers. However, the clinicopathological implication of miR-23b-3p in hepatocellular carcinoma (HCC) remains unclear. Our study evaluated the role of miR-23b-3p in HCC and investigated its potential application as a marker for preliminary diagnosis and therapy in HCC. High-throughput data from the NCBI Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) were collected and analyzed. One hundred and one tissue sections of HCC were paired with adjacent non-cancerous HCC as further supplements. miR-23b-3p expression was detected using quantitative real-time PCR. Additionally, the relationship between miR-23b-3p expression and HCC progression and Time-to-recurrence (months) was explored. Ten algorithms were applied to predict the prospective target genes of miR-23b-3p. Next, we conducted bioinformatics analysis for further study. miR-23b-3p expression was pronouncedly decreased in HCC tissues in contrast with their paired adjacent non-cancerous HCC (P<0.001) with RT-qPCR. In total, 405 targets, acquired with consistent prediction from at least five databases, were used for the bioinformatics analysis. According to the Gene Ontology (GO) analysis, all targets were classified into biological processes, cellular components and molecular functions. In the pathway analysis, targets of miR-23b-3p were primarily enriched in the signaling pathways of renal cell carcinoma, hepatitis B and pancreatic cancer (corrected P-value <0.05). In the protein-protein interaction (PPI) network for miR-23b-3p, a total of 8 targets, including SRC, AKT1, EGFR, CTNNB1, BCL2, SMAD3, PTEN and KDM6A, were located in the key nodes with high degree (>35). In conclusion, this study provides impressive illumination of the potential role of miR-23b-3p in HCC tumorigenesis and progression. Furthermore, miR-23b-3p may act as a predictor of HCC and could be a new treatment target.

Project description:MicroRNAs (miRNAs/miRs) have been reported to be closely associated with numerous human diseases, including cholangiocarcinoma (CCA). However, the number of miRNAs known to be involved in CCA is limited, and the association between miR?132?3p and CCA remains unknown. In the present study, the clinical role of miR?132?3p and its potential signaling pathways were investigated by multiple approaches. Reverse transcription?quantitative PCR (RT?qPCR), CCA?associated Gene Expression Omnibus (GEO), ArrayExpress and Sequence Read Archive (SRA) miRNA?microarray or miRNA?sequencing data were screened, and meta?analyses were conducted, in order to calculate the receiver operating characteristic (ROC) curve and standardized mean difference (SMD). The predicted target genes of miR?132?3p were obtained from 12 online databases and were combined with the downregulated differentially expressed genes identified in the RNA?sequencing data of CCA. Gene Ontology annotation and pathway analysis were performed in WebGestalt. Protein?protein interaction analyses were conducted in STRING. The Cancer Genome Atlas (TCGA) mRNA expression profiles were used to validate the expression levels of hub genes at the mRNA level. The Human Protein Atlas was used to identify the protein expression levels of hub genes in CCA tissues and non?tumor biliary epithelium. The meta?analyses comprised 10 groups of RT?qPCR data, eight GEO microarray datasets and one TCGA miRNA?sequencing dataset. The SMD of miR?132?3p in CCA was 0.75 (95% CI: 0.25, 1.24), which indicated that miR?132?3p was overexpressed in CCA tissues. This finding was supported by a summary ROC value of 0.80 (95% CI: 0.76, 0.83). The pooled sensitivity and specificity were 0.81 (95% CI: 0.59, 0.93) and 0.71 (95% CI: 0.58, 0.81), respectively. The relative expression level of miR?132?3p in the early stage of CCA (stages I?II) was 6.8754±0.5279, which was markedly lower than that in the advanced stage (stages III?IVB), 7.3034±0.3267 (P=0.003). Consistently, the miR?132?3p level in low?grade CCA (grades G1?G2) was 6.7581±0.5297, whereas it was 7.1191±0.4651 in patients with high?grade CCA (grades G3?G4) (P=0.037). Furthermore, 555 potential target genes of miR?132?3p in CCA were mainly enriched in the 'Focal Adhesion?PI3K?Akt?mTOR?signaling pathway'. In conclusion, upregulation of miR?132?3p may serve a pivotal role in the tumorigenesis and progression of CCA by targeting different pathways. Further in vitro and in vivo studies are required to support the current findings.

Dataset Information

Clinical significance of miR-1180-3p in hepatocellular carcinoma: a study based on bioinformatics analysis and RT-qPCR validation.

Publications

Clinical significance of miR-1180-3p in hepatocellular carcinoma: a study based on bioinformatics analysis and RT-qPCR validation.

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