The ELEANOR noncoding RNA expression contributes to cancer dormancy and predicts late recurrence of estrogen receptor-positive breast cancer.

Autor: Fukuoka M; Division of Cancer Biology, The Cancer Institute of JFCR, Tokyo, Japan.; Division of Surgical Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan., Ichikawa Y; Division of Cancer Biology, The Cancer Institute of JFCR, Tokyo, Japan., Osako T; Division of Pathology, The Cancer Institute of JFCR, Tokyo, Japan.; Department of Pathology, The Cancer Institute Hospital of JFCR, Tokyo, Japan., Fujita T; Division of Cancer Biology, The Cancer Institute of JFCR, Tokyo, Japan., Baba S; Division of Pathology, The Cancer Institute of JFCR, Tokyo, Japan.; Department of Pathology, The Cancer Institute Hospital of JFCR, Tokyo, Japan.; Pathology Project for Molecular Targets, The Cancer Institute of JFCR, Tokyo, Japan., Takeuchi K; Division of Pathology, The Cancer Institute of JFCR, Tokyo, Japan.; Department of Pathology, The Cancer Institute Hospital of JFCR, Tokyo, Japan.; Pathology Project for Molecular Targets, The Cancer Institute of JFCR, Tokyo, Japan., Tsunoda N; Division of Surgical Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan., Ebata T; Division of Surgical Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan., Ueno T; Breast Oncology Center, The Cancer Institute Hospital of JFCR, Tokyo, Japan., Ohno S; Breast Oncology Center, The Cancer Institute Hospital of JFCR, Tokyo, Japan., Saitoh N; Division of Cancer Biology, The Cancer Institute of JFCR, Tokyo, Japan.
Jazyk: angličtina
Zdroj: Cancer science [Cancer Sci] 2022 Jul; Vol. 113 (7), pp. 2336-2351. Date of Electronic Publication: 2022 May 03.
DOI: 10.1111/cas.15373
Abstrakt: The recurrence risk of estrogen receptor (ER)-positive breast cancer remains high for a long period of time, unlike other types of cancer. Late recurrence reflects the ability of cancer cells to remain dormant through various events, including cancer stemness acquisition, but the detailed mechanism is unknown. ESR1 locus enhancing and activating noncoding RNAs (ELEANORS) are a cluster of nuclear noncoding RNAs originally identified in a recurrent breast cancer cell model. Although their functions as chromatin regulators in vitro are well characterized, their roles in vivo remain elusive. In this study, we evaluated the clinicopathologic features of ELEANORS, using primary and corresponding metastatic breast cancer tissues. The ELEANOR expression was restricted to ER-positive cases and well-correlated with the ER and progesterone receptor expression levels, especially at the metastatic sites. ELEANORS were detected in both primary and metastatic tumors (32% and 29%, respectively), and frequently in postmenopausal cases. Interestingly, after surgery, patients with ELEANOR-positive primary tumors showed increased relapse rates after, but not within, 5 years. Multivariate analysis showed that ELEANORS are an independent recurrence risk factor. Consistently, analyses with cell lines, mouse xenografts, and patient tissues revealed that ELEANORS upregulate a breast cancer stemness gene, CD44, and maintain the cancer stem cell population, which could facilitate tumor dormancy. Our findings highlight a new role of nuclear long noncoding RNAs and their clinical potential as predictive biomarkers and therapeutic targets for late recurrence of ER-positive breast cancer.
(© 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)
Databáze: MEDLINE
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