<p>UBE2T promotes proliferation via G2/M checkpoint in hepatocellular carcinoma</p>

Abstract

BackgroundGrowing evidence suggests that the ubiquitin-proteasome system is involved in the pathogenesis and recurrence of hepatocellular carcinoma (HCC); yet, little is known about the role of ubiquitin-conjugating enzyme E2T (UBE2T) in HCC.Materials and methodsUBE2T levels were detected in HCC tissues and hepatoma cell lines using quantitative reserve transcriptase-polymerase chain reaction and Western blot analysis. Next, the changes of phenotypes after UBE2T knockdown or overexpression were evaluated using in vitro methods. Finally, the mechanism of UBE2T in HCC was tested using ex vivo and in vivo methods.ResultsIn the present study, we reported that UBE2T mRNA and protein levels were significantly upregulated in HCC tissues compared to adjacent non-tumor tissues. Additionally, suppression of UBE2T expression inhibited proliferation, colony formation, tumorigenesis, migration, and invasion of hepatoma cells, whereas UBE2T overexpression led to the opposite outcomes. Moreover, suppression of UBE2T expression resulted in an increase in G2/M phase and a decrease in the percentage of cells in G1 phase, which indicated a cell cycle arrest at the G2/M phase. In contrast, the percentage of cells in G2/M phase decreased following UBE2T overexpression. Further study indicated that UBE2T regulated the G2/M transition by modulating cyclin B1 and cyclin-dependent kinase 1.ConclusionTaken together, the findings of the present study uncover biological functions of UBE2T in hepatoma cells, and delineate preliminary molecular mechanisms of UBE2T in modulating HCC development and progression.

UBE2T is upregulated, predicts poor prognosis, and promotes cell proliferation and invasion via inhibiting autophagy in ovarian cancer

“…Furthermore, the oncogenic roles of UBE2T closely depend on their enzymatic activity. UBE2T can inactivate p53 and BRAC1, promote proliferation of hepatocellular carcinoma and breast cancer cells via directly catalyzing their mono-ubiquitination [11,32]. Consistently, UBE2T knockdown inhibited AKT/mTOR and exerted notably inhibitory effects on growth, proliferation, and invasion of OC cells.…”

“…Furthermore, UBE2T is upregulated in gastric cancer tissues and cells, positively associated with poor differentiation, advanced T stage, and short OS time in patients with gastric cancer [9,10]. Accordingly, UBE2T upregulation, severing as a poor prognostic biomarker, has been con rmed in nasopharyngeal carcinoma [20], osteosarcoma [16], lung cancer [13,14], breast cancer [16], prostate and hepatocellular cancer [11,12,17,26]. Consistently, we demonstrated that UBE2T mRNA and protein was upregulated in OC tissues and cells and UBE2T upregulation was associated with stages and poor prognosis OC patients.…”

“…By inhibiting AKT and related pathways, UBE2T depletion remarkably suppresses cell proliferation, migration, and invasion of osteosarcoma [30], nasopharyngeal carcinoma [15], liver cancer [12], and renal cell carcinoma [18]. Besides, the suppressive roles of UBE2T knockdown on bladder cancer and hepatocellular carcinoma are mainly caused by apoptosis [31] and cell cycle arrest [11]. Furthermore, the oncogenic roles of UBE2T closely depend on their enzymatic activity.…”

“…Recently, the roles of UBE2T have been revealed in cancers. Upregulation of UBE2T, severing as an unfavorable prognostic indicator, has been con rmed in both solid tumors, such as gastric cancer [9,10], hepatocellular carcinoma [11,12], breast cancer [13], lung cancer [13,14], nasopharyngeal carcinoma [15], osteosarcoma [16], prostate cancer [17] and renal cell carcinoma [18], and non-solid tumor like multiple myeloma (MM) [19]. Consistently, UBE2T depletion notably suppresses malignant progression via modulation the activity AKT [18] and p53 [12].…”

Increased expression of UBE2T predicting poor survival of ovarian cancer: based on comprehensive analysis of UBE2s, clinical samples and the GEO database

“…Multiple evidence indicates that UBE2T acts as an oncogene in a variety of tumors, but its molecular mechanism of action varies in different types of cancer. One study showed that UBE2T plays a role in the proliferation and invasion of hepatocellular carcinoma cells by regulating the G2/M transition of the cell cycle through the cyclin B1-CDK1 pathway [55], while another study found that UBE2T enhances p53 ubiquitination and degradation, promoting the carcinogenesis of hepatocellular carcinoma [10]. Furthermore, UBE2T downregulation reduces the activity of the PI3K/Akt signaling pathway, thus inhibiting the proliferation and migration of renal cell carcinoma [51] and osteosarcoma cells [56].…”