Cr(VI)化合物已确认为人类致癌物。Maternally expression 3（MEG3）是第一个被确认为肿瘤抑制基因的长非编码RNA。MEG3在各种人类原发性肿瘤组织和癌细胞系中经常被下调或丧失。MEG3的下调与癌症的发生、进展和转移有关。我们先前的研究发现，在Cr(VI)转化细胞中MEG3丧失，NEDD9上调，与通过相应通道的正常BEAS-2B细胞相比。MEG3的过表达会降低NEDD9的表达。Cr(VI)转化细胞中β-连环蛋白被激活，而MEG3过表达或NEDD9沉默会抑制β-连环蛋白的活化。本研究的结果表明，异白藜芦醇（ISO）处理能够抑制Cr(VI)转化细胞的增殖、迁移和侵袭。进一步研究表明，ISO处理降低了Cr(VI)转化细胞中细胞增殖的生物标志物Ki67的水平，以及细胞周期调节蛋白cyclin D1的水平。ISO回升了Cr(VI)转化细胞中MEG3的表达水平。DNA甲基转移酶DNMT3a、DNMT3b和DNMT1的水平在ISO处理后减少。ISO处理降低了NEDD9的mRNA和蛋白水平。此外，ISO处理还减少了β-连环蛋白的活化。Cr(VI)转化细胞中Slug被上调，E-Cadherin被下调，而ISO处理减少了Slug的表达并增加了E-Cadherin的表达。这项研究证明了ISO是一种有效的抗Cr(VI)诱导的肺癌治疗药物。版权所有 © 2023。Elsevier Inc.发表。

Cr(VI) compounds are confirmed human carcinogens. Maternally expression 3 (MEG3) is the first long non-coding RNA to be identified as a tumor suppressor. MEG3 is frequently downregulated or lost in various primary human tumor tissues and cancer cell lines. Downregulation of MEG3 is associated with cancer initiation, progression, and metastasis. Our previous study has revealed that MEG3 was lost and NEDD9 was upregulated in Cr(VI)-transformed cells compared to those in passage-matched normal BEAS-2B cells. Overexpression of MEG3 reduced NEDD9. β-Catenin was activated in Cr(VI)-transformed cells, overexpression of MEG3 or knockdown of NEDD9 inhibited the activation of β-Catenin. The results from the present study showed that isorhapontigenin (ISO) treatment is able to suppress cell proliferation, migration, and invasion of Cr(VI)-transformed cells. Further study showed that ISO treatment in Cr(VI)-transformed cells decreases the levels of Ki67, a biomarker for cell proliferation, and of cyclin D1, a regulator for the cell cycle. ISO elevated the MEG3 expression level in Cr(VI)-transformed cells. The DNA methylation transferases DNMT3a, DNMT3b, and DNMT1 levels were reduced upon ISO treatment. ISO treatment decreased both mRNA and protein levels of NEDD9. In addition, ISO treatment reduced the activation of β-catenin. Slug was upregulated and While E-Cadherin was downregulated in Cr(VI)-transformed cells, treatment with ISO decreased Slug and increased E-Cadherin. This study demonstrated that ISO is a potent therapeutical agent against lung cancer induced by Cr(VI).Copyright © 2023. Published by Elsevier Inc.