Deletion of mdig enhances H3K36me3 and metastatic potential of the triple negative breast cancer cells

IF 4.1 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES iScience Pub Date : 2022-10-21 DOI:10.1016/j.isci.2022.105057

Chitra Thakur , Yiran Qiu , Qian Zhang , Nicholas J. Carruthers , Miaomiao Yu , Zhuoyue Bi , Yao Fu , Priya Wadgaonkar , Bandar Almutairy , Akimasa Seno , Paul M. Stemmer , Fei Chen

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引用次数: 3

Abstract

In this report, we provide evidence showing diminished expression of the mineral dust-induced gene (mdig), a previously identified oncogenic gene, in human triple negative breast cancer (TNBC). Using a mouse model of orthotopic xenograft of the TNBC MDA-MB-231 cells, we demonstrate that mdig promotes the growth of primary tumors but inhibits metastasis of these cells in vivo. Knockout of mdig resulted in an enhancement of H3K36me3 in the genome and upregulation of some X chromosome-linked genes for cell motility, invasion, and metastasis. Silencing MAGED2, one of the most upregulated and H3K36me3-enriched genes resulted from mdig depletion, can partially reverse the invasive migration of the mdig knockout cells. The anti-metastatic and inhibitory role of mdig on H3K36me3 was cross-validated in another cell line, A549 lung cancer cells. Together, our data suggest that mdig is antagonist against H3K36me3 that enforces expression of genes, such as MAGED2, for cell invasion and metastasis.

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mdig的缺失增强了三阴性乳腺癌细胞的H3K36me3和转移潜能

在本报告中，我们提供的证据表明，矿物粉尘诱导基因(mdig)的表达减少，这是一种以前发现的致癌基因，在人类三阴性乳腺癌(TNBC)中。通过原位移植TNBC MDA-MB-231细胞的小鼠模型，我们证明了mdig促进原发肿瘤的生长，但抑制这些细胞的体内转移。敲除mdig导致基因组中H3K36me3的增强和一些X染色体相关基因的上调，这些基因与细胞运动、侵袭和转移有关。MAGED2是mdig缺失导致的表达上调最多且h3k36me3富集的基因之一，沉默MAGED2可以部分逆转mdig敲除细胞的侵袭性迁移。mdig对H3K36me3的抗转移和抑制作用在另一个细胞系A549肺癌细胞中得到了交叉验证。综上所述，我们的数据表明mdig是H3K36me3的拮抗剂，该拮抗剂可以增强MAGED2等基因的表达，从而促进细胞侵袭和转移。

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来源期刊

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

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