Upregulation of UBE2Q1 via gene copy number gain in hepatocellular carcinoma promotes cancer progression through β-catenin-EGFR-PI3K-Akt-mTOR signaling pathway

Bin Zhang, Chao Deng, Lei Wang, Fan Zhou, Shu Zhang, Wei Kang, Ping Zhan, Juan Chen, Shanshan Shen, Huimin Guo, Ming Zhang, Yi Wang, Feng Zhang, Wei Zhang, Jiangqiang Xiao, Bo Kong, Helmut Friess, Yuzheng Zhuge, Hongli Yan, Xiaoping Zou

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Hepatocellular carcinoma (HCC) is the most common type of liver cancer and represents a highly malignant tumor with a poor prognosis. Therapeutic modalities for HCC are limited and generally ineffective. UBE2Q1 is a putative E2 ubiquitin conjugating enzyme, and has been shown to be overexpressed in various types of cancers including HCC. How UBE2Q1 contributes to hepatocarcinogenesis remains unknown. Here, we show that UBE2Q1 is up-regulated in HCC cell lines and in a subset of human HCC tissues. Up-regulation of UBE2Q1 in primary HCC tumors was significantly correlated with shorter overall survival and disease-free survival. Mechanistically, we showed that the frequent up-regulation of UBE2Q1 in HCCs was attributed to the recurrent UBE2Q1 gene copy gain at chromosome 1q21. Functionally, we showed that knockdown of UBE2Q1 reduced HCC cell proliferation, promoted apoptosis via induction of GADD45α, and suppressed orthotopic tumorigenicity both in vitro and in vivo. Inactivation of UBE2Q1 also impeded HCC cell migration and invasion in vitro through regulating EMT process, and suppressed HCC metastasis in vivo. Interestingly, our data revealed a role of UBE2Q1 in the regulation of β-catenin-EGFR-PI3K-Akt-mTOR signaling pathway. Our findings indicate that UBE2Q1 is a candidate oncogene involved in HCC development and progression and therefore a potential therapeutic target in applicable HCC patients.

Original languageEnglish
Pages (from-to)201-215
Number of pages15
JournalMolecular Carcinogenesis
Volume57
Issue number2
DOIs
StatePublished - Feb 2018
Externally publishedYes

Keywords

  • UBE2Q1
  • apoptosis
  • copy number gain
  • hepatocellular carcinoma
  • proliferation

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