Kruppel-like factor 12 suppresses bladder cancer growth through transcriptionally inhibition of enolase 2

Kruppel-like factors (KLFs) are transcription factors and play important roles in bladder cancer (BC). Clarifying the function of KLFs will provide new strategies for clinical treatment of BC. In this study, we found that Kruppel-like factor 12 (KLF12) was decreased in BC tissues and cells. Knockdown of KLF12 by siRNA dramatically elevated the proliferation and colony formation of BC cells. By contrast, overexpressing KLF12 suppressed the cell viability and the number of clones. Overexpression of KLF12 also regulated cell cycle progression, apoptosis and migration of BC cells. Furthermore, KLF12 bound to the promoter of enolase 2 (ENO2) and transcriptionally inhibited the expression of ENO2, which was highly expressed in BC tissues. KLF12 suppressed, while ENO2 promoted glycolysis. Lastly, ENO2 overexpression and knockdown promoted and suppressed the proliferation and migration of BC cells, respectively. These results suggest that KLF12 acts as a tumor suppressor by negatively regulated ENO2. Targeting ENO2 is a promising treatment strategy for this malignancy .

Automated summary

KLF12 was found to be decreased in bladder cancer tissues and cells, and its downregulation was associated with increased proliferation, colony formation, and migration of cancer cells. KLF12 acts as a tumor suppressor by negatively regulating ENO2, which promotes glycolysis in bladder cancer cells. Targeting ENO2 could be a promising treatment strategy for this malignancy.