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

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.

Zhang 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 ... -  《-》

Small nucleolar RNA ACA11 promotes proliferation, migration and invasion in hepatocellular carcinoma by targeting the PI3K/AKT signaling pathway.

Emerging evidence suggests that tumorigenesis involves dysregulation of small nucleolar RNAs (snoRNAs). However, the role of small nucleolar RNA ACA11 (ACA11) in the development of hepatocellular carcinoma (HCC) remains unknown. Expression of ACA11 was measured using quantitative RT-PCR in 92 HCC specimens and 7 HCC cell lines. We found that ACA11 expression was significantly upregulated in HCC tissues and hepatoma cell lines. This upregulation of ACA11 in HCC tumors was significantly associated with histological grade, HBV infection, Barcelona Clinic Liver Cancer stage, portal vein tumor thrombus and poorer patient survival. Knockdown of ACA11 induced G0/G1 phase arrest and suppressed proliferation, migration and invasion of HCCLM9 and SK-Hep1 cells. Low ACA11 expression resulted in decreased HCC growth in an animal model. Conversely, transgenic expression of ACA11 induced S phase progression and enhanced proliferation, migration and invasion of Huh7 cells in vitro and in vivo. Finally, we found that ACA11 promoted cell growth, migration and invasion through activation of the PI3K/AKT pathway, subsequently increasing cyclinD1 expression and inducing EMT. These results suggest that ACA11 has an oncogenic role in HCC and may serve as a promising prognostic biomarker and therapeutic target for patients with HCC.

Wu L ，Zheng J ，Chen P ，Liu Q ，Yuan Y ... -  《-》

[EEF1A2 inhibits the p53 function in hepatocellular carcinoma via PI3K/AKT/mTOR-dependent stabilization of MDM4].

Longerich T 《-》

Overexpression of microRNA-133b is associated with the increased survival of patients with hepatocellular carcinoma after curative hepatectomy: Involvement of the EGFR/PI3K/Akt/mTOR signaling pathway.

Wang X ，Zeng J ，Wang L ，Zhang X ，Liu Z ，Zhang H ，Dong J ... -  《-》

DUXAP10 inhibition attenuates the proliferation and metastasis of hepatocellular carcinoma cells by regulation of the Wnt/β-catenin and PI3K/Akt signaling pathways.

The long non-coding RNA DUXAP10 has been involved in the development, progression, and metastasis in several human cancers, but its biological function and underlying mechanism in hepatocellular carcinoma (HCC) still undetermined. The present study was proposed to explore the effect of DUXAP10 on the growth and metastasis of HCC cells and the potential mechanisms involved. The results showed that DUXAP10 is dramatically elevated in HCC tumor tissues and cell lines. Knockdown of DUXAP10 by DUXAP10 si-RNA significantly inhibited the cell viability, proliferation and induce the apoptosis of HCC cell line. Meanwhile, inhibition of DUXAP10 attenuates the cell migration, invasion, and epithelial-mesenchymal transition (EMT) process. No significant change of JNK MAPK pathway was detected in DUXAP10 siRNA transfected HCC cell lines. The β-catenin and pAkt levels were decreased in the Hep G2+DUXAP10 siRNA and SMMC7721+DUXAP10 siRNA groups, while the activation of Wnt/β-catenin or PI3K/Akt suppressed the inhibition of DUXAP10 siRNA on cell proliferation and migration. Collectively, DUXAP10 plays a critical role in regulating HCC development, potentially by regulating EMT and cell proliferation through the PI3K/Akt and Wnt/β-catenin signaling. Inhibition of DUXAP10 in HCC HepG2 cells could attenuate the EMT and cell proliferation and invasion. Therefore, DUXAP10 might be a promising therapy target to inhibit the growth of HCC.

Han K ，Li C ，Zhang X ，Shang L ... -  《-》