Medical Oncology

, 32:149 | Cite as

Ubiquitin-conjugating enzyme E2C regulates apoptosis-dependent tumor progression of non-small cell lung cancer via ERK pathway

  • Zhongmian Zhang
  • Ping Liu
  • Jian Wang
  • Tianxiao Gong
  • Fang Zhang
  • Jun Ma
  • Na HanEmail author
Original Paper


The oncogenic role of ubiquitin-conjugating enzyme E2C (UBE2C) had been identified in some types of human tumors, while the clinical and biological role of UBE2C in non-small cell lung cancer (NSCLC) is still elusive. Here, we have determined the specific role of UBE2C in NSCLC. Western blot and qRT-PCR were used for detecting the mRNA level and protein level of UBE2C in NSCLC samples and cell lines, respectively. Lentivirus product was used to conduct loss of function assay. qRT-PCR array was employed to detect potential downstream genes regulated by UBE2C. As the result, UBE2C mRNA level was approximately threefold overexpression in NSCLC tissues compared with normal tissues, while a sharp change was detected at protein level. Overexpression of UBE2C in lung cancer samples was correlated with advanced pathological stage. UBE2C regulated cell growth in an apoptosis-dependent way. PCR Array analysis revealed that UBE2C regulated the expression of genes associated with tumor growth, apoptosis, and angiogenesis. Furthermore, UBE2C could regulate phospho-ERK1/2 level but not STAT3, YAP, or AKT pathway, which was accompanied with the classic function of ERK pathway in cell growth and apoptosis. In conclusion, our results indicated UBE2C might be a novel therapeutic target in NSCLC.


NSCLC UBE2C Apoptosis ERK pathway 



This study was supported by Science and Technology Research Project of Henan province (132102310355) and the Science and Technology Research Project of Jinshui district in 2014 (201433).

Conflict of interest


Supplementary material

12032_2015_609_MOESM1_ESM.xlsx (10 kb)
Supplementary material 1 (XLSX 9 kb)


  1. 1.
    Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014;64:9–29.CrossRefPubMedGoogle Scholar
  2. 2.
    Travis WD, Brambilla E, Noguchi M, Nicholson AG, Geisinger K, et al. International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society: international multidisciplinary classification of lung adenocarcinoma: executive summary. Proc Am Thorac Soc. 2011;8:381–5.CrossRefPubMedGoogle Scholar
  3. 3.
    Shaid S, Brandts C, Serve H, Dikic I. Ubiquitination and selective autophagy. Cell Death Differ. 2013;20:21–30.CrossRefPubMedCentralPubMedGoogle Scholar
  4. 4.
    Pickart CM. Mechanisms underlying ubiquitination. Ann Rev Biochem. 2001;70:503–33.CrossRefPubMedGoogle Scholar
  5. 5.
    Hock AK, Vousden KH. The role of ubiquitin modification in the regulation of p53. Biochim Biophys Acta (BBA). 2014;1843:137–49.CrossRefGoogle Scholar
  6. 6.
    Burger AM, Seth AK. The ubiquitin-mediated protein degradation pathway in cancer: therapeutic implications. Eur J Cancer. 2004;40:2217–29.CrossRefPubMedGoogle Scholar
  7. 7.
    Loussouarn D, Campion L, Leclair F, Campone M, Charbonnel C, et al. Validation of UBE2C protein as a prognostic marker in node-positive breast cancer. Br J Cancer. 2009;101:166–73.CrossRefPubMedCentralPubMedGoogle Scholar
  8. 8.
    Chen S, Chen Y, Hu C, Jing H, Cao Y, et al. Association of clinicopathological features with UbcH10 expression in colorectal cancer. J Cancer Res Clin Oncol. 2010;136:419–26.CrossRefPubMedGoogle Scholar
  9. 9.
    Bavi P, Uddin S, Ahmed M, Jehan Z, Bu R, et al. Bortezomib stabilizes mitotic cyclins and prevents cell cycle progression via inhibition of UBE2C in colorectal carcinoma. Am J Pathol. 2011;178:2109–20.CrossRefPubMedCentralPubMedGoogle Scholar
  10. 10.
    Ieta K, Ojima E, Tanaka F, Nakamura Y, Haraguchi N, et al. Identification of overexpressed genes in hepatocellular carcinoma, with special reference to ubiquitin-conjugating enzyme E2C gene expression. Int J Cancer. 2007;121:33–8.CrossRefPubMedGoogle Scholar
  11. 11.
    Kadara H, Lacroix L, Behrens C, Solis L, Gu X, et al. Identification of gene signatures and molecular markers for human lung cancer prognosis using an in vitro lung carcinogenesis system. Cancer Prev Res. 2009;2:702–11.CrossRefGoogle Scholar
  12. 12.
    Takezawa K, Okamoto I, Nishio K, Jänne PA, Nakagawa K. Role of ERK-BIM and STAT3-survivin signaling pathways in ALK inhibitor–induced apoptosis in EML4-ALK–positive lung cancer. Clin Cancer Res. 2011;17:2140–8.CrossRefPubMedGoogle Scholar
  13. 13.
    Scrima M, De Marco C, Fabiani F, Franco R, Pirozzi G, et al. Signaling networks associated with AKT activation in non-small cell lung cancer (NSCLC): new insights on the role of phosphatydil-inositol-3 kinase. PLoS One. 2012;7:e30427.CrossRefPubMedCentralPubMedGoogle Scholar
  14. 14.
    Yang C-L, Liu Y-Y, Ma Y-G, Xue Y-X, Liu D-G, et al. Curcumin blocks small cell lung cancer cells migration, invasion, angiogenesis, cell cycle and neoplasia through Janus kinase-STAT3 signalling pathway. PLoS One. 2012;7:e37960.CrossRefPubMedCentralPubMedGoogle Scholar
  15. 15.
    Lin C-W, Chang Y-L, Chang Y-C, Lin J-C, Chen C-C, et al. MicroRNA-135b promotes lung cancer metastasis by regulating multiple targets in the Hippo pathway and LZTS1. Nat Commun. 2013;4:1877.CrossRefPubMedGoogle Scholar
  16. 16.
    Hao Z, Zhang H, Cowell J. Ubiquitin-conjugating enzyme UBE2C: molecular biology, role in tumorigenesis, and potential as a biomarker. Tumor Biol. 2012;33:723–30.CrossRefGoogle Scholar
  17. 17.
    Wagner KW, Sapinoso LM, Frierson HF, Butz N, Mestan J, et al. Overexpression, genomic amplification and therapeutic potential of inhibiting the UbcH10 ubiquitin conjugase in human carcinomas of diverse anatomic origin. Oncogene. 2004;23:6621–9.CrossRefPubMedGoogle Scholar
  18. 18.
    Berlingieri M, Pallante P, Guida M, Nappi C, Masciullo V, et al. UbcH10 expression may be a useful tool in the prognosis of ovarian carcinomas. Oncogene. 2007;26:2136–40.CrossRefPubMedGoogle Scholar
  19. 19.
    Farhat FS, Tfayli A, Fakhruddin N, Mahfouz R, Otrock ZK, et al. Expression, prognostic and predictive impact of VEGF and bFGF in non-small cell lung cancer. Crit Rev Oncol Hematol. 2012;84:149–60.CrossRefPubMedGoogle Scholar
  20. 20.
    Zhao M, Gao F-H, Wang J-Y, Liu F, Yuan H-H, et al. JAK2/STAT3 signaling pathway activation mediates tumor angiogenesis by upregulation of VEGF and bFGF in non-small-cell lung cancer. Lung Cancer. 2011;73:366–74.CrossRefPubMedGoogle Scholar
  21. 21.
    Kim SJ, Rabbani ZN, Dewhirst MW, Vujaskovic Z, Vollmer RT, et al. Expression of HIF-1α, CA IX, VEGF, and MMP-9 in surgically resected non-small cell lung cancer. Lung Cancer. 2005;49:325–35.CrossRefPubMedGoogle Scholar
  22. 22.
    Cox G, Jones JL, O’Byrne KJ. Matrix metalloproteinase 9 and the epidermal growth factor signal pathway in operable non-small cell lung cancer. Clin Cancer Res. 2000;6:2349–55.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Zhongmian Zhang
    • 1
  • Ping Liu
    • 1
  • Jian Wang
    • 1
  • Tianxiao Gong
    • 1
  • Fang Zhang
    • 1
  • Jun Ma
    • 1
  • Na Han
    • 1
    Email author
  1. 1.Department of Oncology, The Second Affiliated Hospital of Zhengzhou UniversityZhengzhou University School of Medicine, Central LaboratoryZhengzhouChina

Personalised recommendations