Open Access

Increased mediator complex subunit 15 expression is associated with poor prognosis in hepatocellular carcinoma

  • Authors:
    • Kunyuan Wang
    • Chenxi Duan
    • Xuejing Zou
    • Yang Song
    • Wenwen Li
    • Lushan Xiao
    • Jie Peng
    • Liheng Yao
    • Qian Long
    • Li Liu
  • View Affiliations

  • Published online on: January 18, 2018     https://doi.org/10.3892/ol.2018.7820
  • Pages: 4303-4313
  • Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: HTML 0 views | PDF 0 views     Cited By (CrossRef): 0 citations

Abstract

Mediator complex subunit 15 (MED15) is a coactivator involved in the regulated transcription of RNA polymerase II‑dependent genes and serves an oncogenic role in numerous types of cancer. However, the expression and function of MED15 in hepatocellular carcinoma (HCC) remain unknown. In the present study, the aim was to investigate the expression and clinical significance of MED15 in HCC. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and immunohistochemical analysis revealed that MED15 mRNA and protein levels were significantly upregulated in HCC tissues compared with those in the corresponding adjacent non‑tumor liver tissues. Furthermore, analyzing data from The Cancer Genome Atlas‑Liver Hepatocellular Carcinoma (TCGA‑LIHC) and GSE14520 datasets revealed a significant correlation between MED15 expression and the tumor size (P=0.033), Barcelona Clinic Liver Cancer stage (P=0.031), α‑fetoprotein levels (P=0.002) and metastasis risk (P=0.001). Furthermore, patients with high MED15 expression levels had a shorter survival time compared with those with low MED15 expression levels (P<0.05). Univariate and multivariate analyses further revealed that MED15 may be an independent prognostic factor for the overall survival of HCC patients (hazard ratio, 1.762; 95% confidence interval, 1.077‑2.882; P<0.05). In addition, MED15 expression was positively associated with hypoxia‑inducible factor 1α expression in the TCGA‑LIHC and GSE14520 datasets (P<0.01). In conclusion, the data reported in the present study indicated that MED15 is overexpressed in HCC and may represent a novel prognostic biomarker for patients with HCC.

References

1 

Sia D, Villanueva A, Friedman SL and Llovet JM: Liver cancer cell of origin, molecular class, and effects on patient prognosis. Gastroenterology. 152:745–761. 2017. View Article : Google Scholar : PubMed/NCBI

2 

Torre LA, Siegel RL, Ward EM and Jemal A: Global cancer incidence and mortality rates and trends-An update. Cancer Epidemiol Biomarkers Prev. 25:16–27. 2016. View Article : Google Scholar : PubMed/NCBI

3 

Llovet JM, Zucman-Rossi J, Pikarsky E, Sangro B, Schwartz M, Sherman M and Gores G: Hepatocellular carcinoma. Nat Rev Dis Primers. 2:160182016. View Article : Google Scholar : PubMed/NCBI

4 

Kato Y, Habas R, Katsuyama Y, Näär AM and He X: A component of the ARC/Mediator complex required for TGF beta/Nodal signalling. Nature. 418:641–646. 2002. View Article : Google Scholar : PubMed/NCBI

5 

Yang F, Vought BW, Satterlee JS, Walker AK, Jim Sun ZY, Watts JL, DeBeaumont R, Saito RM, Hyberts SG, Yang S, et al: An ARC/Mediator subunit required for SREBP control of cholesterol and lipid homeostasis. Nature. 442:700–704. 2006. View Article : Google Scholar : PubMed/NCBI

6 

Zhao M, Yang X, Fu Y, Wang H, Ning Y, Yan J, Chen YG and Wang G: Mediator MED15 modulates transforming growth factor beta (TGFβ)/Smad signaling and breast cancer cell metastasis. J Mol Cell Biol. 5:57–60. 2013. View Article : Google Scholar : PubMed/NCBI

7 

Yang X and Yang F: Mediating lipid biosynthesis: Implications for cardiovascular disease. Trends Cardiovasc Med. 23:269–273. 2013. View Article : Google Scholar : PubMed/NCBI

8 

Nakatsubo T, Nishitani S, Kikuchi Y, Iida S, Yamada K, Tanaka A and Ohkuma Y: Human mediator subunit MED15 promotes transcriptional activation. Drug Discov Ther. 8:212–217. 2014. View Article : Google Scholar : PubMed/NCBI

9 

Berti L, Mittler G, Przemeck GK, Stelzer G, Günzler B, Amati F, Conti E, Dallapiccola B, Hrabé de Angelis M, Novelli G and Meisterernst M: Isolation and characterization of a novel gene from the DiGeorge chromosomal region that encodes for a mediator subunit. Genomics. 74:320–332. 2001. View Article : Google Scholar : PubMed/NCBI

10 

Shaikhibrahim Z, Offermann A, Halbach R, Vogel W, Braun M, Kristiansen G, Bootz F, Wenzel J, Mikut R, Lengerke C, et al: Clinical and molecular implications of MED15 in head and neck squamous cell carcinoma. Am J Pathol. 185:1114–1122. 2015. View Article : Google Scholar : PubMed/NCBI

11 

Shaikhibrahim Z, Menon R, Braun M, Offermann A, Queisser A, Boehm D, Vogel W, Rüenauver K, Ruiz C, Zellweger T, et al: MED15, encoding a subunit of the mediator complex, is overexpressed at high frequency in castration-resistant prostate cancer. Int J Cancer. 135:19–26. 2014. View Article : Google Scholar : PubMed/NCBI

12 

Offermann A, Vlasic I, Syring I, Vogel W, Ruiz C, Zellweger T, Rentsch CA, Hagedorn S, Behrends J, Nowak M, et al: MED15 overexpression in prostate cancer arises during androgen deprivation therapy via PI3K/mTOR signaling. Oncotarget. 8:7964–7976. 2017. View Article : Google Scholar : PubMed/NCBI

13 

Klümper N, Syring I, Offermann A, Shaikhibrahim Z, Vogel W, Müller SC, Ellinger J, Strauß A, Radzun HJ, Ströbel P, et al: Differential expression of Mediator complex subunit MED15 in testicular germ cell tumors. Diagn Pathol. 10:1652015. View Article : Google Scholar : PubMed/NCBI

14 

Schiano C, Casamassimi A, Rienzo M, de Nigris F, Sommese L and Napoli C: Involvement of Mediator complex in malignancy. Biochim Biophys Acta. 1845:66–83. 2014.PubMed/NCBI

15 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

16 

Ovchinnikov DA, Wan Y, Coman WB, Pandit P, Cooper-White JJ, Herman JG and Punyadeera C: DNA methylation at the novel CpG sites in the promoter of MED15/PCQAP gene as a biomarker for head and neck cancers. Biomarker Insights. 9:53–60. 2014. View Article : Google Scholar : PubMed/NCBI

17 

Gañán-Gómez I, Wei Y, Yang H, Boyano-Adánez MC and García-Manero G: Oncogenic functions of the transcription factor Nrf2. Free Radic Biol Med. 65:750–764. 2013. View Article : Google Scholar : PubMed/NCBI

18 

Luo D, Wang Z and Wu J, Jiang C and Wu J: The role of hypoxia inducible factor-1 in hepatocellular carcinoma. Biomed Res Int. 2014:4092722014. View Article : Google Scholar : PubMed/NCBI

19 

Monga SP: β-catenin signaling and roles in liver homeostasis, injury, and tumorigenesis. Gastroenterology. 148:1294–1310. 2015. View Article : Google Scholar : PubMed/NCBI

20 

Rogacki K, Kasprzak A and Stępiński A: Alterations of Wnt/β-catenin signaling pathway in hepatocellular carcinomas associated with hepatitis C virus. Pol J Pathol. 1:9–21. 2015. View Article : Google Scholar

21 

Li H, Wang W, Liu X, Paulson KE, Yee AS and Zhang X: Transcriptional factor HBP1 targets P16(INK4A), upregulating its expression and consequently is involved in Ras-induced premature senescence. Oncogene. 29:5083–5094. 2010. View Article : Google Scholar : PubMed/NCBI

22 

Semenza GL: Defining the role of hypoxia-inducible factor 1 in cancer biology and therapeutics. Oncogene. 29:625–634. 2010. View Article : Google Scholar : PubMed/NCBI

23 

Liao D and Johnson RS: Hypoxia: A key regulator of angiogenesis in cancer. Cancer Metastasis Rev. 26:281–290. 2007. View Article : Google Scholar : PubMed/NCBI

24 

Wu XZ, Xie GR and Chen D: Hypoxia and hepatocellular carcinoma: The therapeutic target for hepatocellular carcinoma. J Gastroenterol Hepatol. 22:1178–1182. 2007. View Article : Google Scholar : PubMed/NCBI

25 

Xiang ZL, Zeng ZC, Fan J, Tang ZY, He J, Zeng HY and Chang JY: The expression of HIF-1α in primary hepatocellular carcinoma and its correlation with radiotherapy response and clinical outcome. Mol Biol Rep. 39:2021–2029. 2012. View Article : Google Scholar : PubMed/NCBI

26 

Lin D and Wu J: Hypoxia inducible factor in hepatocellular carcinoma: A therapeutic target. World J Gastroenterol. 21:12171–12178. 2015. View Article : Google Scholar : PubMed/NCBI

Related Articles

Journal Cover

April 2018
Volume 15 Issue 4

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

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Wang, K., Duan, C., Zou, X., Song, Y., Li, W., Xiao, L. ... Liu, L. (2018). Increased mediator complex subunit 15 expression is associated with poor prognosis in hepatocellular carcinoma. Oncology Letters, 15, 4303-4313. https://doi.org/10.3892/ol.2018.7820
MLA
Wang, K., Duan, C., Zou, X., Song, Y., Li, W., Xiao, L., Peng, J., Yao, L., Long, Q., Liu, L."Increased mediator complex subunit 15 expression is associated with poor prognosis in hepatocellular carcinoma". Oncology Letters 15.4 (2018): 4303-4313.
Chicago
Wang, K., Duan, C., Zou, X., Song, Y., Li, W., Xiao, L., Peng, J., Yao, L., Long, Q., Liu, L."Increased mediator complex subunit 15 expression is associated with poor prognosis in hepatocellular carcinoma". Oncology Letters 15, no. 4 (2018): 4303-4313. https://doi.org/10.3892/ol.2018.7820