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Long Non-coding RNA NR2F1-AS1 Induces Breast Cancer Dormancy in Lungs by Regulating NR2F1 and ΔNp63

ABSTRACT: Long Non-coding RNA NR2F1-AS1 Induces Breast Cancer Dormancy in Lungs by Regulating NR2F1 and ΔNp63

PROVIDER: PRJNA627846 | ENA |

REPOSITORIES: ENA

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Long Non-coding RNA NR2F1-AS1 Induces Breast Cancer Dormancy in Lungs by Regulating NR2F1 and ΔNp63

Project description:We show that the epithelial-like and mesenchymal-like subpopulations of breast cancer stem-like cells (BCSCs) demonstrate different levels dormancy and tumorigenicity in lungs. The long non-coding RNA (lncRNA) molecule NR2F1-AS1 (NAS1) is up-regulated in the dormant BCSC subpopulation, and functionally promotes tumor dissemination but reduces proliferation in lungs. Mechanically, NAS1 promotes internal ribosome entry site (IRES)-mediated NR2F1 translation, leading to inhibition of ΔNp63 transcription by NR2F1. Further, ΔNp63 downregulation results in epithelial-mesenchymal transition, reduced tumorigenicity and enhanced dormancy of cancer cells in lungs.

2023-04-23 | GSE149265 | GEO

Late recurrence-associated long non-coding RNA NR2F1 antisense 1 (NR2F1-AS1)

Project description:Long non-coding RNA NR2F1 antisense RNA1 (lncRNA NR2F1-AS1) was identified as the main candidate associated to late recurrence in ER-positive breast cancer clinical samples. Gain-of-function of NR2F1-AS1 induced the expression of dormancy-inducers BMP4 and DEC2, and upregulated pluripotency markers NANOG and OCT4. Representative pathways entailed to metastatic events such as HER2/Neu, hypoxia, EMT and inflammatory-response were also found enriched.

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Project description:Our data showed that NR2F1-AS1 functions oncogenic roles in gastric cancer (GC), but the underlying molecular mechanism remains largely unknown to date. To explore the function of lncRNA NR2F1-AS1 in gastric cancer, loss-of-function and RNA sequencing studies were performed in SGC7901 cell line. The results showed that depletion of NR2F1-AS1 significantly decreased the expression of VAMP7. Interestingly, VAMP7 was also a target gene of miR-29a-3p. Our data showed that NR2F1-AS1 promotes GC progression through regulating miR-29a/VAMP7 axis.

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

Project description: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.

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Project description:Late recurrence-associated long non-coding RNA NR2F1 antisense 1 (NR2F1-AS1) II

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Knockdown of lncRNA NR2F1-AS1 in gastric cancer cells

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Disrupted transcripitonal network in ΔNp63 AEC tissue model

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Effects of SOCS2-AS1 inhibition in prostate cancer cells

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