Krüppel-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 Krüppel-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.

Krüppel样因子（KLFs）是转录因子，在膀胱癌（BC）中起重要作用。阐明KLF的功能将为BC的临床治疗提供新的策略。在这项研究中，我们发现BC组织和细胞中的Krüppel样因子12（KLF12）减少。siRNA敲低KLF12大大提高了BC细胞的增殖和集落形成。相比之下，过表达KLF12抑制细胞活力和克隆数。KLF12的过表达还调节细胞周期进程，BC细胞凋亡和迁移。此外，KLF12与烯醇化酶2（ENO2）的启动子结合并转录抑制ENO2的表达，该表达在BC组织中高度表达。KLF12抑制，而ENO2促进糖酵解。最后，ENO2的过表达和敲低分别促进和抑制BC细胞的增殖和迁移。这些结果表明，KLF12通过负调控的ENO2起到抑癌作用。靶向ENO2是针对这种恶性肿瘤的有前途的治疗策略。