Knockdown of pyruvate kinase M2 suppresses bladder cancer progression
Author:
Luo Guang-Cheng12, Xu Ran1, Zhang Xi1, Xu Lin2, Zhao Xiao-Kun3, Wang Xin-Jun12
Affiliation:
1. Department of Urology, Zhongshan Hospital Xiamen University, School of Medicine , Xiamen University , Xiamen , Fujian , China 2. The School of Clinical Medicine , Fujian Medical University , Fuzhou , Fujian , China 3. Department of Urology , The Second Xiangya Hospital, Central South University , Changsha , Hunan , China
Abstract
Abstract
Objectives
Bladder cancer (BCa) is one of the most frequently diagnosed cancers of the urinary tract and has a high mortality. The M2 splice isoform of pyruvate kinase (PKM2) is a key regulator of the Warburg effect in cancer cells. This study aimed to evaluate metabolic alterations and biological behaviours after knocking down PKM2.
Methods
In this study, 36 pairs of BCa tissues and adjacent normal tissues were collected to analyse the expression level of PKM2 and to explore the relationship between PKM2 level and tumour and patient status. After PKM2 knockdown in T24 cells, cell survival, migration, invasion, glucose uptake, lactate production, and apoptosis were detected. The tumour-forming ability of PKM2-reducing T24 cells was examined in vivo.
Results
The results showed that PKM2 expression correlates with BCa stage and grade. PKM2 knockdown decreases glucose consumption and lactate production and suppresses cell proliferation, migration, and invasion while increasing reactive oxygen species levels and apoptosis in T24 BCa cells in vitro. In nude mouse models, PKM2 knockdown reduced xenograft and orthotopic tumour size. Moreover, PKM2 knockdown decreased vimentin and fibronectin expression and increased E-cadherin expression. Analysis of high-throughput sequencing data revealed that PKM2 may also be associated with biological processes and diseases.
Conclusions
Overall, these results indicate that PKM2 may be a therapeutic target for BCa patients.
Funder
Natural Science Foundation of Fujian Province Project of Science and Technology Bureau of Xiamen The Young/Middle-aged Talent Cultivation Project funded by Fujian Provincial Health and Family Planning Commission and Xiamen Health and Family planning Commission
Publisher
Walter de Gruyter GmbH
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