| Reactivation of tumour suppressor in breast cancer by enhancer switching through NamiRNA network | |
Liang, Ying; Lu, Qi; Li, Wei ; Zhang, Dapeng; Zhang, Fanglin; Zou, Qingping; Chen, Lu; Tong, Ying; Liu, Mengxing; Wang, Shaoxuan; Li, Wenxuan; Ren, Xiaoguang; Xu, Peng; Yang, Zhicong; Dong, Shihua; Zhang, Baolong; Huang, Yanni; Li, Daqiang; Wang, Hailin; Yu, Wenqiang
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| 2021-09-07 | |
| Source Publication | NUCLEIC ACIDS RESEARCH
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| ISSN | 0305-1048 |
| Volume | 49Issue:15Pages:8556-8572 |
| Abstract | Dysfunction of Tumour Suppressor Genes (TSGs) is a common feature in carcinogenesis. Epigenetic abnormalities including DNA hypermethylation or aberrant histone modifications in promoter regions have been described for interpreting TSG inactivation. However, in many instances, how TSGs are silenced in tumours are largely unknown. Given that miRNA with low expression in tumours is another recognized signature, we hypothesize that low expression of miRNA may reduce the activity of TSG related enhancers and further lead to inactivation of TSG during cancer development. Here, we reported that low expression of miRNA in cancer as a recognized signature leads to loss of function of TSGs in breast cancer. In 157 paired breast cancer and adjacent normal samples, tumour suppressor gene GPER1 and miR-339 are both downregulated in Luminal A/B and Triple Negative Breast Cancer subtypes. Mechanistic investigations revealed that miR-339 upregulates GPER1 expression in breast cancer cells by switching on the GPER1 enhancer, which can be blocked by enhancer deletion through the CRISPR/Cas9 system. Collectively, our findings reveal novel mechanistic insights into TSG dysfunction in cancer development, and provide evidence that reactivation of TSG by enhancer switching may be a promising alternative strategy for clinical breast cancer treatment. |
| Department | 环境化学与生态毒理学国家重点实验室 |
| WOS Research Area | Biochemistry & Molecular Biology |
| Document Type | 期刊论文 |
| Identifier | https://ir.rcees.ac.cn/handle/311016/45824 |
| Collection | 环境化学与生态毒理学国家重点实验室 |
| Affiliation | 1.Fudan Univ, Huashan Hosp, Shanghai Publ Hlth Clin Ctr, Canc Metastasis Inst, Shanghai 200032, Peoples R China 2.Fudan Univ, Huashan Hosp, Dept Gen Surg, Canc Metastasis Inst, Shanghai 200032, Peoples R China 3.Fudan Univ, Shanghai Med Coll, Inst Biomed Sci, Lab RNA Epigenet, Shanghai 200032, Peoples R China 4.Fudan Univ, Jinshan Hosp, Dept Gynaecol, Shanghai 201508, Peoples R China 5.Chinese Acad Sci, Res Ctr Ecoenvironm Sci, State Key Lab Environm Chem & Ecotoxicol, Beijing 100085, Peoples R China 6.Fudan Univ, Shanghai Canc Ctr, Shanghai 200032, Peoples R China |
| Recommended Citation GB/T 7714 | Liang, Ying,Lu, Qi,Li, Wei,et al. Reactivation of tumour suppressor in breast cancer by enhancer switching through NamiRNA network[J]. NUCLEIC ACIDS RESEARCH,2021,49(15):8556-8572. |
| APA | Liang, Ying.,Lu, Qi.,Li, Wei.,Zhang, Dapeng.,Zhang, Fanglin.,...&Yu, Wenqiang.(2021).Reactivation of tumour suppressor in breast cancer by enhancer switching through NamiRNA network.NUCLEIC ACIDS RESEARCH,49(15),8556-8572. |
| MLA | Liang, Ying,et al."Reactivation of tumour suppressor in breast cancer by enhancer switching through NamiRNA network".NUCLEIC ACIDS RESEARCH 49.15(2021):8556-8572. |
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| Reactivation of tumo（6268KB） | 期刊论文 | 出版稿 | 开放获取 | CC BY-NC-SA | View Application Full Text | |
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