报告题目：Nuclear non-coding RNAs contributing to 3D genome structure and tumor dormancy in breast cancer

报告嘉宾：Pr. Noriko Saitoh

主 持 人：翁杰敏教授

报告时间：2024年5月20日 下午13：30-14：30

报告地点：生科楼534小会议室

报告人简介：

Noriko Saitoh,

Chief

The Cancer Institute of JFCR

Division of Cancer Biology, Tokyo, Japan                                                              

EDUCATION

1996              Ph. D. in Johns Hopkins University, School of Medicine, BCMB

CAREER

1996-1998      Postdoctoral Fellow, NIH/NIDDK, Maryland, USA

1998-2001      Postdoctoral Fellow, Cold Spring Harbor Laboratory, New York, USA

2001-2002      Postdoctoral Fellow, Kyushu University, School of Medicine, Japan      

2002-2006      Postdoctoral Fellow, Kumamoto University, IMEG, Japan

2006-2013      Assistant Professor, Kumamoto University, IMEG, Japan

2013-2017      Associate Professor, Kumamoto University, IMEG, Japan

2017-present  Chief, The Cancer Institute of JFCR, Japan

报告简介：

Most nuclear long non-coding RNAs (lncRNAs) are expressed in a cell type- or disease-specific manner. They often function as epigenetic factors, and are involved in higher-order chromatin. Dysregulation of lncRNAs often results in diseases, but the detailed mechanisms remain to be investigated.

We have identified ELEANORS, a cluster of lncRNAs in a model of endocrine therapy-resistant estrogen receptor (ER)-positive breast cancer, the LTED (long-term estrogen deprivation) cells. ELEANORS are transcribed from a large chromatin domain including the gene encoding ER, ESR1. They form a molecular condensate, the ELEANOR cloud, which is required for ESR1 gene activation. C-technologies, including Hi-C, revealed that ELEANORS define a chromatin domain, TAD (topologically associating domain) of about 0.7 Mb. They also equilibrate cell growth and apoptosis by mediating a long-range chromatin interaction of the ESR1 and FOXO3 genes. These suggest that ELEANORS are involved in 3D genome structure.

Analysis of clinicopathologic features of ELEANORS using patient tissues revealed that ELEANOR expression in primary tumors positively correlates with late recurrence. Further, we found that ELEANORS are involved in transcription activation of the CD44 gene, a cancer stem cell marker. The ELEANOR and CD44 genes were frequently co-localized in the LTED cells. Our results suggest that the chromatin regulation by nuclear lncRNAs may represent a pathological mechanism, and lncRNAs may serve as diagnostic markers and therapeutic targets for late recurrence of breast cancer.