Long non-coding NR2F1-AS1 is associated with tumor recurrence in estrogen receptor-positive breast cancers
Autor: | Ai Hironaka-Mitsuhashi, Tomofumi Yamamoto, Fumitaka Takeshita, Anna Sanchez Calle, Yumi Kawamura, Kenji Tamura, Yusuke Yamamoto, Takahiro Ochiya, Akihiko Shimomura, Hitoshi Tsuda, Makiko Ono |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Cancer Research dormancy Transcription Genetic Cell Estrogen receptor Breast Neoplasms lcsh:RC254-282 03 medical and health sciences Mice 0302 clinical medicine Breast cancer lncRNA Downregulation and upregulation Cell Line Tumor Genetics medicine late recurrence Animals Humans Neoplasm Metastasis Research Articles business.industry Gene Expression Profiling Cell Cycle Cancer General Medicine medicine.disease lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Gene Expression Regulation Neoplastic 030104 developmental biology medicine.anatomical_structure Oncology Receptors Estrogen Hormone receptor 030220 oncology & carcinogenesis Cancer cell Cancer research PR/ER transcriptional complex Molecular Medicine Biomarker (medicine) Female RNA Long Noncoding Neoplasm Recurrence Local business Receptors Progesterone Research Article ER‐positive breast cancer |
Zdroj: | Molecular Oncology Molecular Oncology, Vol 14, Iss 9, Pp 2271-2287 (2020) |
ISSN: | 1878-0261 |
Popis: | The tenacity of late recurrence of estrogen receptor (ER)‐positive breast cancer remains a major clinical issue to overcome. The administration of endocrine therapies within the first 5 years substantially minimizes the risk of relapse; however, some tumors reappear 10–20 years after the initial diagnosis. Accumulating evidence has strengthened the notion that long noncoding RNAs (lncRNAs) are associated with cancer in various respects. Because lncRNAs may display high tissue/cell specificity, we hypothesized this might provide new insights to tumor recurrence. By comparing transcriptome profiles of 24 clinical primary tumors obtained from patients who developed distant metastases and patients with no signs of recurrence, we identified lncRNA NR2F1‐AS1 whose expression was associated with tumor recurrence. We revealed the relationship between NR2F1‐AS1 and the hormone receptor expressions in ER‐positive breast cancer cells. Gain of function of NR2F1‐AS1 steered cancer cells into quiescence‐like state by the upregulation of dormancy inducers and pluripotency markers, and activates representative events of the metastatic cascade. Our findings implicated NR2F1‐AS1 in the dynamics of tumor recurrence in ER‐positive breast cancers and introduce a new biomarker that holds a therapeutic potential, providing favorable prospects to be translated into the clinical field. We identified the long noncoding RNA NR2F1‐AS1 in the dynamics of tumor recurrence in ER‐positive breast cancers. NR2F1‐AS1 steers cancer cells into quiescence‐like state by the upregulation of dormancy inducers and pluripotency markers, and activates the metastatic cascade. Its expression is mediated by the PR/ER transcriptional complex bringing favorable prospects for developing new therapeutic strategies and introducing a new biomarker. |
Databáze: | OpenAIRE |
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