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Reduced expression of microRNA‑139‑5p in hepatocellular carcinoma results in a poor outcome: An exploration the roles of microRNA‑139‑5p in tumorigenesis, advancement and prognosis at the molecular biological level using an integrated meta‑analysis and bioinformatic investigation

  • Authors:
    • Hui Qin
    • Dong‑Yue Wen
    • Qiao Que
    • Chuan‑Yang Zhou
    • Xiao‑Dong Wang
    • Yu‑Ting Peng
    • Yun He
    • Hong Yang
    • Bo‑Ming Liao

  • View Affiliations

  • Published online on: November 1, 2019     https://doi.org/10.3892/ol.2019.11031
  • Pages: 6704-6724

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

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Abstract

Hepatocellular carcinoma (HCC) is generally considered one of the most common gastrointestinal malignant tumors, characterized by high invasiveness and metastatic rate, as well as insidious onset. A relationship between carcinogenicity and aberrant microRNA‑139‑5p (miR‑139‑5p) expression has been identified in multiple tumors while the specific molecular mechanisms of miR‑139‑5p in HCC have not yet been thoroughly elucidated. A meta‑analysis of available data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus, ArrayExpress and Oncomine databases, as well as the published literature, was comprehensively conducted with the aim of examining the impact of miR‑139‑5p expression on HCC. Additionally, predicted downstream target genes were confirmed using a series of bioinformatics tools. Moreover, a correlative biological analysis was performed to ascertain the precise function of miR‑139‑5p in HCC. The results revealed that the expression of miR‑139‑5p was noticeably lower in HCC compared with non‑tumor liver tissues according to the pooled standard mean difference, which was ‑0.84 [95% confidence interval (CI): ‑1.36 to ‑0.32; P<0.001]. Furthermore, associations were detected between miR‑139‑5p expression and certain clinicopathological characteristics of TCGA samples, including tumor grade, pathological stage and T stage. Moreover, the pooled hazard ratio (HR) for overall survival (HR=1.37; 95% CI: 1.07‑1.76; P=0.001) indicated that decreased miR‑139‑5p expression was a risk factor for adverse outcomes. Additionally, 382 intersecting genes regulated by miR‑139‑5p were obtained and assembled in signaling pathways, including ‘transcription factor activity, sequence‑specific DNA binding’, ‘pathways in cancer’ and ‘Ras signaling pathway’. Notably, four targeted genes that were focused in ‘pathways in cancer’ were identified as hub genes and immunohistochemical staining of the proteins encoded by these four hub genes in liver tissues, explored using the Human Protein Atlas database, confirmed their expression patterns in HCC and normal liver tissues Findings of the present study suggest that reduced miR‑139‑5p expression is capable of accelerating tumor progression and is associated with a poor clinical outcome by modulating the expression of downstream target genes involved in tumor‑associated signaling pathways.
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December-2019
Volume 18 Issue 6

Print ISSN: 1792-1074
Online ISSN:1792-1082

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  • CiteScore: 5.7
  • CiteScore Rank: Q2: #139/404 Oncology
  • Source Normalized Impact per Paper (SNIP): 0.574
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Spandidos Publications style
Qin H, Wen DY, Que Q, Zhou CY, Wang XD, Peng YT, He Y, Yang H and Liao BM: Reduced expression of microRNA‑139‑5p in hepatocellular carcinoma results in a poor outcome: An exploration the roles of microRNA‑139‑5p in tumorigenesis, advancement and prognosis at the molecular biological level using an integrated meta‑analysis and bioinformatic investigation. Oncol Lett 18: 6704-6724, 2019.
APA
Qin, H., Wen, D., Que, Q., Zhou, C., Wang, X., Peng, Y. ... Liao, B. (2019). Reduced expression of microRNA‑139‑5p in hepatocellular carcinoma results in a poor outcome: An exploration the roles of microRNA‑139‑5p in tumorigenesis, advancement and prognosis at the molecular biological level using an integrated meta‑analysis and bioinformatic investigation. Oncology Letters, 18, 6704-6724. https://doi.org/10.3892/ol.2019.11031
MLA
Qin, H., Wen, D., Que, Q., Zhou, C., Wang, X., Peng, Y., He, Y., Yang, H., Liao, B."Reduced expression of microRNA‑139‑5p in hepatocellular carcinoma results in a poor outcome: An exploration the roles of microRNA‑139‑5p in tumorigenesis, advancement and prognosis at the molecular biological level using an integrated meta‑analysis and bioinformatic investigation". Oncology Letters 18.6 (2019): 6704-6724.
Chicago
Qin, H., Wen, D., Que, Q., Zhou, C., Wang, X., Peng, Y., He, Y., Yang, H., Liao, B."Reduced expression of microRNA‑139‑5p in hepatocellular carcinoma results in a poor outcome: An exploration the roles of microRNA‑139‑5p in tumorigenesis, advancement and prognosis at the molecular biological level using an integrated meta‑analysis and bioinformatic investigation". Oncology Letters 18, no. 6 (2019): 6704-6724. https://doi.org/10.3892/ol.2019.11031