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  • Long non-coding RNA NR2F1-AS1 induces breast cancer lung metastatic dormancy by regulating NR2F1 and ΔNp63.

Long non-coding RNA NR2F1-AS1 induces breast cancer lung metastatic dormancy by regulating NR2F1 and ΔNp63.

Nature communications (2021-09-04)
Yingjie Liu, Peiyuan Zhang, Qiuyao Wu, Houqin Fang, Yuan Wang, Yansen Xiao, Min Cong, Tingting Wang, Yunfei He, Chengxin Ma, Pu Tian, Yajun Liang, Lun-Xiu Qin, Qingcheng Yang, Qifeng Yang, Lujian Liao, Guohong Hu
ABSTRACT

Disseminated tumor cells often fall into a long term of dormant stage, characterized by decreased proliferation but sustained survival, in distant organs before awakening for metastatic growth. However, the regulatory mechanism of metastatic dormancy and awakening is largely unknown. Here, we show that the epithelial-like and mesenchymal-like subpopulations of breast cancer stem-like cells (BCSCs) demonstrate different levels of dormancy and tumorigenicity in lungs. The long non-coding RNA (lncRNA) NR2F1-AS1 (NAS1) is up-regulated in the dormant mesenchymal-like BCSCs, and functionally promotes tumor dissemination but reduces proliferation in lungs. Mechanistically, NAS1 binds to NR2F1 mRNA and recruits the RNA-binding protein PTBP1 to promote internal ribosome entry site (IRES)-mediated NR2F1 translation, thus leading to suppression of ΔNp63 transcription by NR2F1. Furthermore, ΔNp63 downregulation results in epithelial-mesenchymal transition, reduced tumorigenicity and enhanced dormancy of cancer cells in lungs. Overall, the study links BCSC plasticity with metastatic dormancy, and reveals the lncRNA as an important regulator of both processes.

MATERIALS
Product Number
Brand
Product Description

Roche
Insulin, human, recombinant (yeast)
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5′/3′ RACE Kit, 2nd Generation, sufficient for 10 reactions
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Biotin RNA Labeling Mix, sufficient for 20 reactions (transcription), pkg of 40 μL, solution
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DIG Northern Starter Kit, suitable for Northern blotting, sufficient for 10 labeling reactions
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Hydrocortisone, Steroid hormone of the adrenal cortex with anti-inflammatory properties.
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hBFGF, FGF-Basic, recombinant, expressed in E. coli, suitable for cell culture
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Heparin sodium salt from porcine intestinal mucosa, Grade I-A, ≥180 USP units/mg, powder, BioReagent, suitable for cell culture
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DAPI, 4′,6-Diamidine-2′-phenylindole dihydrochloride