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Correlation between down-expression of miR-431 and clinicopathological significance in HCC tissues

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Abstract

Background and aims

Researches have shown that miRNAs have been proposed as novel diagnostic biomarkers for classification and prognostic stratification of HCC. However, whether or not miR-431 contributes to the progression of HCC remains unknown. Therefore, we aimed to investigate the clinicopathological significance of miR-431 in HCC.

Methods

MiR-431 expression in 95 HCC cases and corresponding adjacent non-cancerous tissues was evaluated by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Furthermore, statistical analysis was performed to identify the correlations between expression of miR-431 and a variety of clinicopathological parameters and patient recurrence. The area under the receiver operating characteristic curve (AUC) was used to evaluate the accuracy of miR-431 as a biomarker for HCC diagnosis and prediction of disease deterioration.

Results

MiR-431 was markedly down-regulated in the HCC samples (1.1885 ± 0.75867) compared with corresponding adjacent tumor tissues (1.7957 ± 0.89333, P < 0.001). The AUC of low miR-431 expression to diagnose HCC was 0.668 (95 % CI 0.592–0.744, P < 0.001). MiR-431 down-expression was correlated with multiple malignant characteristics, including lymph node metastasis (r = −0.455, P < 0.001), clinical TNM stage (r = −0.223, P = 0.030), MTDH (r = −0.292, P = 0.006), vaso-invasion (r = −0.204, P = 0.047), MVD (r = −0.281, P = 0.006) and HCV (r = 0.215, P = 0.037). Additionally, the recurrent time of lower miR-431 expression group was 56.602 ± 3.914 months, much longer than that in the high expression group (50.009 ± 2.731 months), however, no significant difference was noted (χ 2 = 0.005, P = 0.943).

Conclusions

The down-expression of miR-431 is partially responsible for a series of clinicopathological features which may be tightly correlated with the progression of HCC. Thus, expression of miR-431 may be proposed as a new factor in association with the progression of HCC.

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References

  1. Hu Q, Lou GG, Liu YC, Qian L, Lv BD. The tumor necrosis factor-alpha-308 and -238 polymorphisms and risk of hepatocellular carcinoma for Asian populations: a meta-analysis. Curr Ther Res Clin Exp. 2014;76:70–5.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  2. McGivern DR, Lemon SM. Virus-specific mechanisms of carcinogenesis in hepatitis C virus associated liver cancer. Oncogene. 2011;30:1969–83.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Ye SL, Takayama T, Geschwind J, Marrero JA, Bronowicki JP. Current approaches to the treatment of early hepatocellular carcinoma. Oncologist. 2010;15(Suppl 4):34–41.

    Article  PubMed  Google Scholar 

  4. Tanaka S, Arii S. Molecular targeted therapies in hepatocellular carcinoma. Semin Oncol. 2012;39:486–92.

    Article  CAS  PubMed  Google Scholar 

  5. Zhao YJ, Ju Q, Li GC. Tumor markers for hepatocellular carcinoma. Mol Clin Oncol. 2013;1:593–8.

    CAS  PubMed Central  PubMed  Google Scholar 

  6. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–97.

    Article  CAS  PubMed  Google Scholar 

  7. He L, Hannon GJ. MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet. 2004;5:522–31.

    Article  CAS  PubMed  Google Scholar 

  8. Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, et al. MicroRNA expression profiles classify human cancers. Nature. 2005;435:834–8.

    Article  CAS  PubMed  Google Scholar 

  9. Elmen J, Lindow M, Schutz S, Lawrence M, Petri A, Obad S, et al. LNA-mediated microRNA silencing in non-human primates. Nature. 2008;452:896–9.

    Article  CAS  PubMed  Google Scholar 

  10. Krutzfeldt J, Rajewsky N, Braich R, Rajeev KG, Tuschl T, Manoharan M, et al. Silencing of microRNAs in vivo with ‘antagomirs’. Nature. 2005;438:685–9.

    Article  PubMed  Google Scholar 

  11. Park JK, Kogure T, Nuovo GJ, Jiang J, He L, Kim JH, et al. miR-221 silencing blocks hepatocellular carcinoma and promotes survival. Cancer Res. 2011;71:7608–16.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Tanaka T, Sugaya S, Kita K, Arai M, Kanda T, Fujii K, et al. Inhibition of cell viability by human IFN-beta is mediated by microRNA-431. Int J Oncol. 2012;40:1470–6.

    CAS  PubMed  Google Scholar 

  13. Fang L, Du WW, Yang X, Chen K, Ghanekar A, Levy G, et al. Versican 3′-untranslated region (3′-UTR) functions as a ceRNA in inducing the development of hepatocellular carcinoma by regulating miRNA activity. FASEB J. 2013;27:907–19.

    Article  CAS  PubMed  Google Scholar 

  14. Chen G, Kronenberger P, Teugels E, Umelo IA, De Greve J. Targeting the epidermal growth factor receptor in non-small cell lung cancer cells: the effect of combining RNA interference with tyrosine kinase inhibitors or cetuximab. BMC Med. 2012;10:28.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Dang Y, Luo D, Rong M, Chen G. Underexpression of miR-34a in hepatocellular carcinoma and its contribution towards enhancement of proliferating inhibitory effects of agents targeting c-MET. PLoS One. 2013;8:e61054.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Rong M, Chen G, Dang Y. Increased miR-221 expression in hepatocellular carcinoma tissues and its role in enhancing cell growth and inhibiting apoptosis in vitro. BMC Cancer. 2013;13:21.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Chen G, Umelo IA, Lv S, Teugels E, Fostier K, Kronenberger P, et al. miR-146a inhibits cell growth, cell migration and induces apoptosis in non-small cell lung cancer cells. PLoS One. 2013;8:e60317.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Wheeler G, Ntounia-Fousara S, Granda B, Rathjen T, Dalmay T. Identification of new central nervous system specific mouse microRNAs. FEBS Lett. 2006;580:2195–200.

    Article  CAS  PubMed  Google Scholar 

  19. Abu-Elneel K, Liu T, Gazzaniga FS, Nishimura Y, Wall DP, Geschwind DH, et al. Heterogeneous dysregulation of microRNAs across the autism spectrum. Neurogenetics. 2008;9:153–61.

    Article  CAS  PubMed  Google Scholar 

  20. Salem AM, Ismail S, Zarouk WA, Abdul Baky O, Sayed AA, Abd El-Hamid S, et al. Genetic variants of neurotransmitter-related genes and miRNAs in Egyptian autistic patients. Sci World J. 2013;2013:670621.

    Article  Google Scholar 

  21. Wu D, Murashov AK. MicroRNA-431 regulates axon regeneration in mature sensory neurons by targeting the Wnt antagonist Kremen1. Front Mol Neurosci. 2013;6:35.

    Article  PubMed Central  PubMed  Google Scholar 

  22. Liu R, Ma X, Xu L, Wang D, Jiang X, Zhu W, et al. Differential microRNA expression in peripheral blood mononuclear cells from Graves’ disease patients. J Clin Endocrinol Metab. 2012;97:E968–72.

    Article  CAS  PubMed  Google Scholar 

  23. Wu MJ, Ke PY, Horng JT. RacGTPase-activating protein 1 interacts with hepatitis C virus polymerase NS5B to regulate viral replication. Biochem Biophys Res Commun. 2014;454:19–24.

    Article  CAS  PubMed  Google Scholar 

  24. Sakamuro D, Furukawa T, Takegami T. Hepatitis C virus nonstructural protein NS3 transforms NIH 3T3 cells. J Virol. 1995;69:3893–6.

    CAS  PubMed Central  PubMed  Google Scholar 

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Acknowledgments

The study was supported partly by the Fund of Guangxi Natural Scientific Research (No. 2013GXNSFBA019191), Guangxi Provincial Health Bureau Scientific Research Project (Z2014054), Youth Science Foundation of Guangxi Medical University (GXMUYSF201311), Guangxi University Science and Technology Research Projects (LX2014075), and the Fund of National Natural Science Foundation of China (NSFC 81360327). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Conflict of interest

We declare no conflicts of interest (both financial and personal).

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Correspondence to G. Chen.

Additional information

L. Pan and F. Ren were contributed equally.

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Pan, L., Ren, F., Rong, M. et al. Correlation between down-expression of miR-431 and clinicopathological significance in HCC tissues. Clin Transl Oncol 17, 557–563 (2015). https://doi.org/10.1007/s12094-015-1278-y

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