Upregulation of UBE2Q1 via gene copy number gain in hepatocellular carcinoma promotes cancer progression through β-catenin-EGFR-PI3K-Akt-mTOR signaling pathway
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AbstractHepatocellular 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.
Acceptance Date29/09/2017
All Author(s) ListZhang B, Deng C, Wang L, Zhou F, Zhang S, Kang W, Zhan P, Chen J, Shen S, Guo H, Zhang M, Wang Y, Zhang F, Zhang W, Xiao J, Kong B, Friess H, Zhuge Y, Yan H, Zou X
Journal nameMolecular Carcinogenesis
Year2018
Month2
Volume Number57
Issue Number2
PublisherWiley
Pages201 - 215
ISSN0899-1987
eISSN1098-2744
LanguagesEnglish-United Kingdom

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