矿物粉尘诱导基因表达缺失可诱发晚期或三阴性乳腺癌的侵袭和转移

　　矿物粉尘诱导基因属于环境诱导基因之一，既往研究已经发现该基因表达可以预测乳腺癌患者总生存。

　　2018年9月21日，英国《自然》旗下《信号转导与靶向疗法》发表美国密歇根韦恩州立大学、加利福尼亚希望之城国家医学中心、中国苏州翔实医药的研究报告，进一步证实矿物粉尘诱导基因对于早期和晚期乳腺癌的不同作用。

　　该研究发现，对于非癌乳腺，矿物粉尘诱导基因是细胞生长和细胞运动的增殖因子。不过，对于乳腺癌，矿物粉尘诱导基因水平较高可以抑制癌细胞的转移和浸润。整体DNA甲基化、染色质可及性、H3K9me3异染色质特征分析表明，沉默矿物粉尘诱导基因可以增强DNA和组蛋白的甲基化。通过免疫染色和数据挖掘，该研究发现非侵袭性或早期乳腺癌的矿物粉尘诱导基因表达显著增加。相反，三阴性和其他侵袭性乳腺癌的矿物粉尘诱导基因表达减少，表明矿物粉尘诱导基因表达缺失可能是侵袭性乳腺癌的重要特征。

　　因此，该研究结果表明，矿物粉尘诱导基因是一种新的生物标志，可能促进早期或非侵袭性乳腺癌生长，同时抑制晚期或三阴性乳腺癌的侵袭和转移，为此类乳腺癌的矿物粉尘诱导基因靶向疗法研发奠定了基础。

Signal Transduct Target Ther. 2018 Sep 21;3:25.

Loss of mdig expression enhances DNA and histone methylation and metastasis of aggressive breast cancer.

Chitra Thakur, Bailing Chen, Lingzhi Li, Qian Zhang, Zeng-Quan Yang, Fei Chen.

Wayne State University, Detroit, MI, USA; Synthesis Medchem Corp, Suzhou, China; City of Hope Institute, Duarte, CA, USA.

We previously reported that expression of an environmentally induced gene, mineral dust-induced gene (mdig), predicts overall survival in breast cancer patients. In the present report, we further demonstrate the differential roles of mdig between earlier- and later-stage breast cancers. In noncancerous breast, mdig is a proliferation factor for cell growth and cell motility. In breast cancer, however, higher levels of mdig negatively regulate the migration and invasion of cancer cells. Assessment of global DNA methylation, chromatin accessibility and H3K9me3 heterochromatin signature suggests that silencing mdig enhances DNA and histone methylation. Through immunostaining and data mining, we found that mdig is significantly upregulated in noninvasive and/or earlier-stage breast cancers. In contrast, in triple-negative and other invasive breast cancers, diminished mdig expression was noted, indicating that the loss of mdig expression could be an important feature of aggressive breast cancers. Taken together, our data suggest that mdig is a new biomarker that likely promotes tumor growth in the early stages of breast cancer while acting as a tumor suppressor to inhibit invasion and metastasis in later-stage tumors.

DOI: 10.1038/s41392-018-0027-4