Upregulation of ubiquitin-conjugating enzyme E2Z is associated with human hepatocellular carcinoma.

UBE2Z, a member of ubiquitin-conjugating enzymes, has been reported to participate in multiple biological processes. However, its roles in hepatocellular carcinoma (HCC) remain undiscovered. This study aimed at investigating the functions of UBE2Z in HCC. Firstly, we evaluated UBE2Z expression in HCC and identified associations among UBE2Z expression, clinicopathological features, copy number alterations, DNA methylation, and survival of patients using data from the Cancer Genome Atlas (TCGA). As a result, UBE2Z was remarkably overexpressed in HCC tissues relative to normal liver tissues (P < 0.05). High UBE2Z expression was significantly correlated with age, advanced TNM stage, histological grade, vascular invasion, elevated serum alpha-fetoprotein expression (AFP), worse overall survival (OS) and disease-free survival (DFS) of HCC patients (all P < 0.05). Besides, data mining in UCSC Xena Browser showed that UBE2Z DNA amplification which was significantly associated with its expression was common (108 out of 364) in HCC, and that the level of UBE2Z DNA methylation was negatively associated with its expression (Pearson's correlation = -0.4, P < 0.0001). After analyzing the datasets from TCGA, we further confirmed the up-regulation of UBE2Z in 60 HCC tissues and several HCC cell lines. Finally, functional assays were performed and showed that knockdown UBE2Z using small interfering RNA (siRNA) could significantly restrain tumor cell proliferation and suppress cell migration and cell invasion through repressing the expression of MMP2 and MMP9. Meanwhile, UBE2Z knockdown could effectively reduce the expression of p-ERK, p-p38, p-JNK, p-Stat3 and p-JAK2, suggesting that UBE2Z might promote HCC progression by targeting ERK and stat3 signaling pathway. These findings implied that UBE2Z might be considered as a prognostic biomarker in HCC and provided a potential therapeutic tumor-associated antigen for HCC.

Quercetin suppresses the chymotrypsin-like activity of proteasome via inhibition of MEK1/ERK1/2 signaling pathway in hepatocellular carcinoma HepG2 cells.

The proteasomal system is a promising target for cancer treatment. Quercetin (Que), a flavonoid compound with antitumor ability, displays the inhibitory effect on proteasome activity. However, the underlying molecular mechanisms are ill defined. The present study found that Que treatment significantly reduced the chymotrypsin-like protease activity of proteasome whereas the trypsin- and caspase-like protease activities remained unchanged in HepG2 cancer cells, along with activation of p38 MAPK and JNK and reduction of ERK1/2 phosphorylation. Que-reduced proteasome activity could not be reverted by inhibition of p38 MAPK and JNK signaling pathway. In addition, MEK1 overexpression or knockdown upregulated or downregulated the chymotrypsin-like protease activity of proteasome, respectively. Both Que and MEK1/ERK1/2 inhibitor attenuated the expression levels of proteasome ß subunits. These results indicate that Que-induced suppression of MEK1/ERK1/2 signaling and subsequent reduction of proteasome ß subunits is responsible for its inhibitory impacts on proteasome activity.

Palladium-catalyzed C-2 selective arylation of quinolines.

An efficient method for the Pd-catalyzed regioselective C-2 arylation of quinolines is presented. Reactions of various substituted quinolines and unactivated arenes have been conducted under mild conditions. The result shows good product yields of 2-arylquinolines, which are highly useful building blocks for the synthesis of bioactive alkaloid natural products and drug molecules.