Abstract

Endometrial cancer (EC) is the most prevalent gynecological malignancy with high mortality. Chemotherapy plays a pivotal role both in an adjuvant setting and in exclusive treatment. However, current pharmacotherapies are limited and not ideal for improving the overall survival of EC patients. Thus, identification of the underlying molecular mechanisms responsible for initiation and progression of EC is imperative for developing novel therapeutic strategies. Ubiquitin C-terminal hydrolase L5 (UCHL5) has been found to aggravate tumor growth and metastasis in several different types of tumor models such as esophageal squamous cell carcinoma, hepatocellular carcinoma, and epithelial ovarian cancer. However, whether UCHL5 influences the growth of EC has not been elucidated. To expose the role of UCHL5 on EC, bioinformatics analysis was conducted, and it hinted that UCHL5 was overexpressed in EC tissues and associated with lower overall survival. Consistently, the overexpression of UCHL5 in EC tissues and cell lines was further confirmed by western blot (WB) and polymerase chain reaction (PCR) compared with non-tumor control. Lentivirus vectors carrying UCHL5 shRNA or CD sequences were used to reduce or overexpress the UCHL5 gene, respectively. Cell proliferation and cycle were facilitated, and cell apoptosis was decreased when the UCHL5 gene was overexpressed in EC cell lines. These results were opposite in UCHL5 knockdown EC cells. Additionally, the expression of β-catenin is positively related to UCHL5 levels and the tumorigenic effects of UCHL5 overexpression were reversed by the Wnt/β-catenin pathway inhibitor XAV939. Thus, Wnt/β-catenin pathway activation may be a partial mechanism responsible for the promoting effects of UCHL5 on EC growth. In conclusion, UCHL5 accelerated the growth of EC via the Wnt/β-catenin pathway and was expected to be an attractive target for EC treatment.

Highlights

  • Endometrial cancer (EC) is the most prevalent invasive gynecological malignancy in the western world and the fourth common cancer in women worldwide, with over 280,000 new cases worldwide in 2017 [1]

  • The results suggested that EC patients with low Ubiquitin C-terminal hydrolase L5 (UCHL5) mRNA levels had markedly higher Overall survival (OS) than those with high UCHL5 mRNA levels (Figure 1B)

  • gene set enrichment analysis (GSEA) enrichment plots showed that enrichment of CTNNB1 was associated with UCHL5 gene (Figure 1C)

Read more

Summary

Introduction

Endometrial cancer (EC) is the most prevalent invasive gynecological malignancy in the western world and the fourth common cancer in women worldwide, with over 280,000 new cases worldwide in 2017 [1]. UCHL5 Promoted the Growth of Endometrial Cancer. 36,000 annually, accounting for 1.8% of all cancer deaths [3]. If without follow-up adjuvant therapies such as chemotherapy or radiotherapy, 10–15% surgical patients will relapse [4]. These recurrent cases have a poor prognosis with a 5-year survival rate less than 15% because of the limited treatment options and resistance to current medications [4, 5]. Deeper molecular mechanisms and targeted drugs deserve further exploration

Methods
Results
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call