Circular RNA circTATDN3 promotes the Warburg effect and proliferation in colorectal cancer

As one of the key metabolic enzymes in the glycolytic pathway, lactate dehydrogenase A (LDHA) might be linked to tumor proliferation by driving the Warburg effect. Circular RNAs (circRNAs) are widely implicated in tumor progression. Here, we report that circTATDN3, a circular RNA that interacts with LDHA, plays a critical role in proliferation and energy metabolism in CRC. We found that circTATDN3 expression was increased in CRC cells and tumor tissues and that high circTATDN3 expression was positively associated with poor postoperative prognosis in CRC patients. Additionally, circTATDN3 promoted the proliferation of CRC cells in vivo and vitro. Mechanistically, circTATDN3 was shown to function as an adaptor molecule that enhances the binding of LDHA to FGFR1, leading to increased LDHA phosphorylation and consequently promoting the Warburg effect. Moreover, circTATDN3 increased the expression of LDHA by sponging miR-511-5p, which synergistically promoted CRC progression and the Warburg effect. In conclusion, circTATDN3 may be a target for the treatment of CRC. •Cancer cell uses glycolysis rather than OXPHOS to supply energy preferentially, which is defined as the Warburg effect.•CircTATDN3 promotes the proliferation of CRC through regulating the Warburg effect in vivo and vitro.•CircTATDN3-driven LDHA activation and the regulation of LDHA expression synergistically promote CRC progression and the Warburg effect.•CircTATDN3 is a potential target in the treatment of CRC.