Abstract
Ubiquitin-conjugating enzyme E2T (UBE2T) functions as an E2 ubiquitin-conjugating enzyme in the ubiquitin-proteasome degradation system and mediates cellular processes, such as cell cycle, proliferation, and differentiation. UBE2T has been considered to be an oncogene in a variety of tumors. However, the oncogenic role of UBE2T in cervical cancer remains unclear. In this study, our results first showed that the expression of UBE2T was higher in both of cervical cancer tissues and cells than that in the normal tissues and cells. Knockdown of UBE2T reduced cervical cancer cell viability and suppressed the proliferation, invasion, and migration. However, overexpression of UBE2T contributed to cervical cancer cell growth and metastasis. Moreover, UBE2T overexpression cervical cancer cells demonstrated enhanced self-renewal capacity with upregulation of SOX2, Oct-4, and Nanog protein. Silencing of UBE2T downregulated protein expression of SOX2, Oct-4, and Nanog in cervical cancer cells reduced self-renewal capacity. Furthermore, ectopic UBE2T expression promoted protein expression of glucose-regulated protein 78 (GRP78) and focal adhesion kinase (FAK) phosphorylation in cervical cancer cells. The knockdown of UBE2T reduced protein expression of GRP78 and FAK phosphorylation. Collectively, UBE2T promoted cervical cancer stem cell traits and exerted an oncogenic role through activation of the GRP78/FAK pathway.
Highlights
Cervical cancer ranks as the fourth leading cause of malignance-related mortality in women worldwide and the third most common cancer [1,2]
Microarray analysis based on GEPIA (Gene Expression Profiling Interactive Analysis) database showed that Ubiquitin-conjugating enzyme E2T (UBE2T) was upregulated in the cervical cancer tissues (n = 306) compared to the normal tissues (n = 13) (Figure 1a)
These results suggested that UBE2T might be related to cervical cancer progression
Summary
Cervical cancer ranks as the fourth leading cause of malignance-related mortality in women worldwide and the third most common cancer [1,2]. The widespread implementation of screening programs has reduced morbidity and mortality of cervical cancer in recent years, it remains a major public health problem, in advanced cases [3]. Recent advancements in therapeutic strategies, such as chemotherapy, surgery, and radiotherapy, have improved patients’ survival rate with primary cervical carcinoma [4]. The advanced cases of cervical cancer with local or distant metastasis reduce the 5-year survival rate to 50% [5]. Since polyubiquitin chains are known to play a key role in the regulation of tumor progression, UBE2T is regarded as a potential therapeutic target for tumors [6]. Study has shown that UBE2T was upregulated in bladder cancer tissues and cell lines, and knockdown of UBE2T reduced the proliferation of bladder cancer cells, induced cell cycle arrest in the G2/M phase, and increased the apoptosis [7]. The role of UBE2T in cervical cancer is still not clear
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