UBE2C Drives Human Cervical Cancer Progression and Is Positively Modulated by mTOR.

An-Jen Chiang,Li-Wen Chen,Jim Jinn-Chyuan Sheu,Yuan-Chin Ivan Chang,Chia-Jung Li,Chung Chang,Kuan-Hao Tsui,Tsung-Hsien Chang

doi:10.3390/biom11010037

Abstract

Cervical cancer is a common gynecological malignancy, accounting for 10% of all gynecological cancers. Recently, targeted therapy for cervical cancer has shown unprecedented advantages. Several studies have shown that ubiquitin conjugating enzyme E2 (UBE2C) is highly expressed in a series of tumors, and participates in the progression of these tumors. However, the possible impact of UBE2C on the progression of cervical squamous cell carcinoma (CESC) remains unclear. Here, we carried out tissue microarray analysis of paraffin-embedded tissues from 294 cervical cancer patients with FIGO/TNM cancer staging records. The results indicated that UBE2C was highly expressed in human CESC tissues and its expression was related to the clinical characteristics of CESC patients. Overexpression and knockdown of UBE2C enhanced and reduced cervical cancer cell proliferation, respectively, in vitro. Furthermore, in vivo experiments showed that UBE2C regulated the expression and activity of the mTOR/PI3K/AKT pathway. In summary, we confirmed that UBE2C is involved in the process of CESC and that UBE2C may represent a molecular target for CESC treatment.

Highlights

Cervical cancer remains an important genital tract malignancy in women, ranking fourth in both incidence and mortality for female malignancies worldwide [1,2]
In different databases of the HPA, we found high-grade staining for Ubiquitin-conjugating enzyme 2C (UBE2C) in CESC patients
In our reCCI-779 has been approved by the US Food and Drug Administration (FDA) as a first-line sults, it was confirmed that CCI-779 reduced the stability of UBE2C protein in a contreatment for patients with advanced refractory renal cell carcinoma [43]

Summary

Introduction

Cervical cancer remains an important genital tract malignancy in women, ranking fourth in both incidence and mortality for female malignancies worldwide [1,2]. In Taiwan, cervical cancer ranked as the eighth most common cancer in females in 2016, with an age-standardized incidence rate of 8.7 per 100,000 women. Human papillomavirus (HPV) infection is considered to be the leading cause of cervical, vulvar, vaginal, anal, oropharyngeal, and penile cancer [4,5]. HPV types 6 and 11 are low-risk or non-oncogenic viruses that can cause benign or low-grade cervical cell abnormalities. The oncogenic impact of HPV type 16/18 is critical; a recent study in Taiwan found that patients with high-grade squamous intraepithelial lesions were highly infected with high-risk HPV types other than HPV 16/18, such as HPV58, Biomolecules 2021, 11, 37.

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