六价铬[Cr(VI)]因其巨大的工业应用而成为最常见的环境污染物之一，但其影响和机制仍有待研究。我们前期的研究表明，Cr(VI)暴露会导致恶性转化和肿瘤发生。这项研究表明，与对照组和亲代细胞相比，接触 Cr(VI) 的工人的血液样本和 Cr-T 细胞中的糖酵解蛋白 HK2 和 LDHA 水平发生了统计学上的显着变化。 HK2和LDHA敲低抑制细胞增殖和血管生成，较高的HK2和LDHA表达水平与肺癌晚期和不良预后相关。我们发现miR-218水平显着降低，并且miR-218直接靶向HK2和LDHA抑制其表达。 miR-218 的过度表达抑制 Cr-T 细胞中的葡萄糖消耗和乳酸产生。进一步研究发现，miR-218通过降低体内HK2和LDHA表达来抑制肿瘤生长和血管生成。 MiR-218 水平与 HK2 和 LDHA 表达水平以及人类肺癌和其他癌症的癌症发展呈负相关。这些结果表明，miR-218/HK2/LDHA 通路对于调节 Cr(VI) 诱导的癌发生和人类癌症发展至关重要。版权所有 © 2024。由 Elsevier Inc. 出版。

Hexavalent chromium [Cr(VI)] is one of the most common environmental contaminants due to its tremendous industrial applications, but its effects and mechanism remain to be investigated. Our previous studies showed that Cr(VI) exposure caused malignant transformation and tumorigenesis. This study showed that glycolytic proteins HK2 and LDHA levels were statistically significant changed in blood samples of Cr(VI)-exposed workers and in Cr-T cells compared to the control subjects and parental cells. HK2 and LDHA knockdown inhibited cell proliferation and angiogenesis, and higher HK2 and LDHA expression levels are associated with advanced stages and poor prognosis of lung cancer. We found that miR-218 levels were significantly decreased and miR-218 directly targeted HK2 and LDHA for inhibiting their expression. Overexpression of miR-218 inhibited glucose consumption and lactate production in Cr-T cells. Further study found that miR-218 inhibited tumor growth and angiogenesis by decreasing HK2 and LDHA expression in vivo. MiR-218 levels were negatively correlated with HK2 and LDHA expression levels and cancer development in human lung and other cancers. These results demonstrated that miR-218/HK2/LDHA pathway is vital for regulating Cr(VI)-induced carcinogenesis and human cancer development.Copyright © 2024. Published by Elsevier Inc.