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Upregulation of miR‑132‑3p in cholangiocarcinoma tissues: A study based on RT‑qPCR, The Cancer Genome Atlas miRNA sequencing, Gene Expression Omnibus microarray data and bioinformatics analyses

  • Authors:
    • Hua‑Yu Wu
    • Shuang Xia
    • An‑Gui Liu
    • Min‑Da Wei
    • Zhong‑Biao Chen
    • Yu‑Xin Li
    • Yu He
    • Min‑Jun Liao
    • Qi‑Ping Hu
    • Shang‑Ling Pan

  • View Affiliations

  • Published online on: October 7, 2019     https://doi.org/10.3892/mmr.2019.10730
  • Pages: 5002-5020

  • Copyright: © Wu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.
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December-2019
Volume 20 Issue 6

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Wu HY, Xia S, Liu AG, Wei MD, Chen ZB, Li YX, He Y, Liao MJ, Hu QP, Pan SL, Pan SL, et al: Upregulation of miR‑132‑3p in cholangiocarcinoma tissues: A study based on RT‑qPCR, The Cancer Genome Atlas miRNA sequencing, Gene Expression Omnibus microarray data and bioinformatics analyses. Mol Med Rep 20: 5002-5020, 2019
APA
Wu, H., Xia, S., Liu, A., Wei, M., Chen, Z., Li, Y. ... Pan, S. (2019). Upregulation of miR‑132‑3p in cholangiocarcinoma tissues: A study based on RT‑qPCR, The Cancer Genome Atlas miRNA sequencing, Gene Expression Omnibus microarray data and bioinformatics analyses. Molecular Medicine Reports, 20, 5002-5020. https://doi.org/10.3892/mmr.2019.10730
MLA
Wu, H., Xia, S., Liu, A., Wei, M., Chen, Z., Li, Y., He, Y., Liao, M., Hu, Q., Pan, S."Upregulation of miR‑132‑3p in cholangiocarcinoma tissues: A study based on RT‑qPCR, The Cancer Genome Atlas miRNA sequencing, Gene Expression Omnibus microarray data and bioinformatics analyses". Molecular Medicine Reports 20.6 (2019): 5002-5020.
Chicago
Wu, H., Xia, S., Liu, A., Wei, M., Chen, Z., Li, Y., He, Y., Liao, M., Hu, Q., Pan, S."Upregulation of miR‑132‑3p in cholangiocarcinoma tissues: A study based on RT‑qPCR, The Cancer Genome Atlas miRNA sequencing, Gene Expression Omnibus microarray data and bioinformatics analyses". Molecular Medicine Reports 20, no. 6 (2019): 5002-5020. https://doi.org/10.3892/mmr.2019.10730