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UCHL3 promotes aerobic glycolysis of pancreatic cancer through upregulating LDHA expression

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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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Data availability

The data analyzed during the current study are available from the corresponding author on reasonable request.

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Author notes

  1. Y. Fan and D. Hu have the same contribution.

Authors and Affiliations

  1. The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen City, 518107, Guangdong Province, China

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

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  1. Y. Fan
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Contributions

DT and YF designed the study. DT, DH, DL and YT, QT and YC performed the experiments. DH, DL and YT contributed to the literature search. QT and YC wrote the initial draft of the manuscript. LD and DT reviewed and edited the manuscript. All authors read and approved the manuscript.

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Correspondence to D. Tang.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animals are involved in this research.

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Fan, Y., Hu, D., Li, D. et al. UCHL3 promotes aerobic glycolysis of pancreatic cancer through upregulating LDHA expression. Clin Transl Oncol 23, 1637–1645 (2021). https://doi.org/10.1007/s12094-021-02565-1

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  • DOI: https://doi.org/10.1007/s12094-021-02565-1

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