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Clinical and Translational Oncology

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01-08-2021 | Pancreatic Cancer | Research Article

UCHL3 promotes aerobic glycolysis of pancreatic cancer through upregulating LDHA expression

Authors: Y. Fan, D. Hu, D. Li, C. Ma, Y. Tang, Q. Tao, L. Deng, D. Tang

Published in: Clinical and Translational Oncology | Issue 8/2021

Abstract

Background

Aerobic glycolysis has a pivotal role in the carcinogenic process. The current understanding of the functional role and mechanism of UCHL3-related aerobic glycolysis in pancreatic cancer is far from comprehensive, therefore requires an in-depth analysis on this aspect.

Methods

In the present research, the expressions of ubiquitin carboxyl-terminal hydrolase L3 (UCHL3), lactate dehydrogenase A (LDHA) and Forkhead box protein M1 (FOXM1) were detected by qRT-PCR, Western blot and immunohistochemistry. The effects of UCHL3 knockdown or overexpression on pancreatic cancer cells were examined by determining cell viability and colony formation. Aerobic glycolysis was assessed according to glucose uptake, lactic acid production, and lactate dehydrogenase (LDH) activity. Dual-luciferase reporter assay was performed to detect LDHA promoter activity.

Results

The results showed that UCHL3 expression was significantly increased in the pancreatic cancer tissues and cells, and that knocking down UCHL3 noticeably inhibited cell viability and aerobic glycolysis. Further investigations revealed that LDHA expression was promoted by UCHL3 and could be reduced by shFOXM1, and that low-expressed LDHA partly reversed the inhibition of aerobic glycolysis induced by overexpressed UCHL3.

Conclusions

To conclude, this study demonstrates that UCHL3 plays a carcinogenic role by promoting aerobic glycolysis in pancreatic cancer, suggesting that UCHL3 may be a potential diagnostic and therapeutic target for the treatment of cancer.

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Title: UCHL3 promotes aerobic glycolysis of pancreatic cancer through upregulating LDHA expression
Authors: Y. Fan
D. Hu
D. Li
C. Ma
Y. Tang
Q. Tao
L. Deng
D. Tang
Publication date: 01-08-2021
Publisher: Springer International Publishing
Keywords: Pancreatic Cancer
Pancreatic Cancer
Published in: Clinical and Translational Oncology / Issue 8/2021
Print ISSN: 1699-048X
Electronic ISSN: 1699-3055
DOI: https://doi.org/10.1007/s12094-021-02565-1

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