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
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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