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Long non-coding RNA MIAT is estrogen-responsive and promotes estrogen-induced proliferation in ER-positive breast cancer cells

Journal Article · · Biochemical and Biophysical Research Communications
 [1];  [2];  [1];  [3];  [4]; ; ;  [1];  [5];  [6]
  1. Department of Medical Oncology, The First Affiliated Hospital, University of South China, Hengyang City, Hunan Province, 421001 (China)
  2. Department of Pharmacy, The First Affiliated Hospital, University of South China, Hengyang City, Hunan Province, 421001 (China)
  3. Department of Histology and Embryology, Laboratory of Reproductive Medicine, University of South China, Hengyang City, Hunan Province (China)
  4. Department of Oncology, Shenzhen Hospital, University of Hong Kong, Shenzhen City, 518000 (China)
  5. Department of Pathology, The First Affiliated Hospital, University of South China, Hengyang City, Hunan Province (China)
  6. Department of Breast and Thyroid Surgery, The Second Affiliated Hospital, University of South China, Hengyang City, Hunan Province (China)

Highlights: • lncRNA MIAT was over-expressed in ER-positive breast cancer tissues and cells. • Breast cancer cell MIAT expression was estrogen-dependent. • lncRNA MIAT promoted breast cancer cell growth. • lncRNA MIAT was required for breast cancer cell cycle progression. Estrogen drives the development and progression of estrogen receptor (ER)-positive breast cancer. However, the detailed mechanism underlying ER-driven carcinogenesis remains unclear despite extensive studies. Previously reports indicated higher expression of long non-coding RNA (lncRNA) myocardial infarction associated transcript (MIAT) in ER-positive breast cancer tissues than in ER-negative tissues. However, the functional relevance of MIAT in ER-positive breast cancer tumorigenesis was poorly understood. Here, we investigated the role of lncRNA MIAT in ER-positive breast cancer cells. MIAT was over-expressed in ER-positive breast cancer tissues and ER-positive breast cancer cell line MCF-7. Activating estrogen signaling by diethylstilbestrol (DES) led to a dose- and time-dependent up-regulation of MIAT in MCF-7 cells that was dependent on ERα, as evidenced by ERα silencing and pharmacological inhibition using ER antagonist ICI 182780. Silencing MIAT decreased DES-induced MCF-7 cell proliferation while overexpressing MIAT increased MCF-7 cell proliferation. Further mechanistic study identified that MIAT was critical for G1 to S phase cell cycle transition. Taken together, these results suggest that lncRNA MIAT is an estrogen-inducible lncRNA and a key regulator in ER-positive breast cancer cell growth. MIAT could serve as a potential biomarker and promising therapeutic target for ER-positive breast cancer.

OSTI ID:
23105705
Journal Information:
Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 1 Vol. 503; ISSN BBRCA9; ISSN 0006-291X
Country of Publication:
United States
Language:
English

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