PLOD2 promotes aerobic glycolysis and cell progression in colorectal cancer by upregulating HK2.

The purpose of the current study is to characterize the expression of procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2), a membrane-bound homodimeric enzyme that specifically hydroxylates lysine in the telopeptide of procollagens, and assess the clinical significance of PLOD2 in colorectal cancer (CRC). Our results showed that PLOD2 was highly expressed in CRC tumor tissues samples and cell lines both in mRNA and protein level. Next, we found that PLOD2 was positively correlated with Grade (p=0.001), T stage (p=0.001), N stage (p<0.001) and an advanced TNM stage (p<0.001). PLOD2 knockdown attenuates CRC cell proliferation, migration and invasion in vitro. Mechanism analysis PLOD2 affected glycolysis by regulating HK2 expression. HK2 reverses the inhibiting effects of PLOD2 knockdown in CRC. Furthermore, the data suggest that PLOD2 could regulate the expression of HK2 via the STAT3 signaling pathway. Survival analysis reveals that high PLOD2 (HR = 3.800, p < 0.001) and HK2 expression (HR = 10.222, p < 0.001) were correlated with overall survival. After analyzing their expression and correlation, PLOD2 was positively correlated with HK2 (r=0.590, p < 0.001). Our findings have uncovered that PLOD2 is a novel regulatory factor of glucose metabolism via controlling HK2 expression in CRC cells, suggesting PLOD2 as a promising therapeutic target for CRC treatment.