The purpose of this study was 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 show that PLOD2 is highly expressed in CRC tumor tissues and cell lines, both at the mRNA and protein levels. Next, we found that PLOD2 was positively correlated with tumor grade (P = 0.001), T stage (P = 0.001), N stage (P < 0.001), and an advanced TNM stage (P < 0.001). Knockdown of PLOD2 attenuated CRC cell proliferation, migration, and invasiveness, in vitro. Our analysis of the mechanism behind the effects of PLOD2 suggests that PLOD2 affected glycolysis by regulating the expression of hexokinase 2 (HK2). HK2 reverses the inhibitory effects of PLOD2 knockdown in CRC. Furthermore, the data suggest that PLOD2 regulates the expression of HK2 via the STAT3 signaling pathway. Survival analysis revealed that high expression levels of PLOD2 (HR = 3.800, P < 0.001) and HK2 expression (HR = 10.222, P < 0.001) correlated with the overall survival rate. After analyzing their expression and correlation, PLOD2 positively correlated with HK2 (r = 0.590, P < 0.001). Our findings have revealed that PLOD2 is a novel regulatory factor in glucose metabolism, exerted via controlling HK2 expression in CRC cells, suggesting PLOD2 as a promising therapeutic target for CRC treatment.

中文翻译：

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PLOD2通过上调HK2促进大肠癌中有氧糖酵解和细胞进程。

这项研究的目的是表征前胶原赖氨酸，2-氧戊二酸5-二加氧酶2（PLOD2）的表达，这是一种膜结合的同型二聚酶，可特异性地羟化赖氨酸在前胶原的端肽中，并评估PLOD2在临床中的临床意义。大肠癌（CRC）。我们的结果表明PLOD2在CRC肿瘤组织和细胞系中均在mRNA和蛋白质水平上高表达。接下来，我们发现PLOD2与肿瘤等级（P = 0.001），T期（P = 0.001），N期（P <0.001）和晚期TNM期（P <0.001）正相关。体外敲除PLOD2可减弱CRC细胞的增殖，迁移和侵袭性。我们对PLOD2影响背后的机制的分析表明，PLOD2通过调节己糖激酶2（HK2）的表达影响糖酵解。HK2逆转了PLOD2敲低对CRC的抑制作用。此外，数据表明PLOD2通过STAT3信号通路调节HK2的表达。生存分析显示PLOD2（HR = 3.800，P <0.001）和HK2表达（HR = 10.222，P <0.001）的高表达水平与总生存率相关。分析它们的表达和相关性后，PLOD2与HK2正相关（r = 0.590，P <0.001）。我们的发现表明PLOD2是葡萄糖代谢中的新型调节因子，通过控制CRC细胞中HK2的表达发挥作用，提示PLOD2作为CRC治疗的有希望的治疗靶点。生存分析显示PLOD2（HR = 3.800，P <0.001）和HK2表达（HR = 10.222，P <0.001）的高表达水平与总生存率相关。分析它们的表达和相关性后，PLOD2与HK2正相关（r = 0.590，P <0.001）。我们的发现表明PLOD2是葡萄糖代谢中的新型调节因子，通过控制CRC细胞中HK2的表达发挥作用，提示PLOD2作为CRC治疗的有希望的治疗靶点。生存分析显示PLOD2（HR = 3.800，P <0.001）和HK2表达（HR = 10.222，P <0.001）的高表达水平与总生存率相关。分析它们的表达和相关性后，PLOD2与HK2正相关（r = 0.590，P <0.001）。我们的发现表明PLOD2是葡萄糖代谢中的新型调节因子，通过控制CRC细胞中HK2的表达发挥作用，提示PLOD2作为CRC治疗的有希望的治疗靶点。