PLOD2 promotes aerobic glycolysis and cell progression in colorectal cancer by upregulating HK2
PLOD2 promotes aerobic glycolysis and cell progression in colorectal cancer by upregulating HK2
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DOI：
10.1139/bcb-2019-0256
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发表时间：
2020-06-01
影响因子：
2.9
通讯作者：
He, Yi
中科院分区：
文献类型：
--
作者：
Du, Wenwu;Liu, Ning;He, Yi
本研究的目的是表征前胶原-赖氨酸，2-氧戊二酸5-双加氧酶2 （PLOD2）的表达，并评估PLOD2在结直肠癌（CRC）中的临床意义。PLOD2是一种膜结合的同质二聚体酶，在前胶原的端肽中特异性羟化赖氨酸。我们的研究结果表明，PLOD2在CRC肿瘤组织和细胞系的mrna和蛋白水平上都是高表达的。接下来，我们发现PLOD2与肿瘤分级（P = 0.001）、T分期（P = 0.001）、N分期（P < 0.001）和TNM晚期（P < 0.001）呈正相关。在体外，敲低PLOD2可减弱结直肠癌细胞的增殖、迁移和侵袭性。我们对PLOD2作用机制的分析表明，PLOD2通过调节己糖激酶2 （HK2）的表达来影响糖酵解。HK2逆转了PLOD2敲低在结直肠癌中的抑制作用。此外，数据表明PLOD2通过STAT3信号通路调节HK2的表达。生存率分析显示，PLOD2高表达（HR = 3.800, P < 0.001）和HK2高表达（HR = 10.222, P < 0.001）与总生存率相关。分析其表达及相关性后，PLOD2与HK2呈正相关（r = 0.590, P < 0.001）。我们的研究结果表明，PLOD2是一种新的糖代谢调节因子，通过控制结直肠癌细胞中HK2的表达来发挥作用，表明PLOD2是结直肠癌治疗的一个有希望的治疗靶点。
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 themRNAand 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.