ESR1-stabilizing long noncoding RNA TMPO-AS1 promotes hormone-refractory breast cancer progression

Yuichi Mitobe, Kazuhiro Ikeda, Takashi Suzuki, Kiyoshi Takagi, Hidetaka Kawabata, Kuniko Horie-Inoue, Satoshi Inouea

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

Acquired endocrine therapy resistance is a significant clinical problem for breast cancer patients. In recent years, increasing attention has been paid to long noncoding RNA (lncRNA) as a critical modulator for cancer progression. Based on RNA-sequencing data of breast invasive carcinomas in The Cancer Genome Atlas database, we identified thymopoietin antisense transcript 1 (TMPO-AS1) as a functional lncRNA that significantly correlates with proliferative biomarkers. TMPO-AS1 positivity analyzed by in situ hybridization significantly correlates with poor prognosis of breast cancer patients. TMPO-AS1 expression was upregulated in endocrine therapy-resistant MCF-7 cells compared with levels in parental cells and was estrogen inducible. Gain and loss of TMPO-AS1 experiments showed that TMPO-AS1 promotes the proliferation and viability of estrogen receptor (ER)-positive breast cancer cells in vitro and in vivo. Global expression analysis using a microarray demonstrated that TMPO-AS1 is closely associated with the estrogen signaling pathway. TMPO-AS1 could positively regulate estrogen receptor 1 (ESR1) mRNA expression by stabilizing ESR1 mRNA through interaction with ESR1 mRNA. Enhanced expression of ESR1 mRNA by TMPO-AS1 could play a critical role in the proliferation of ER-positive breast cancer. Our findings provide a new insight into the understanding of molecular mechanisms underlying hormone-dependent breast cancer progression and endocrine resistance.

Original languageEnglish
Article numbere00261-19
JournalMolecular and cellular biology
Volume39
Issue number23
DOIs
Publication statusPublished - 2019 Dec 1

Keywords

  • Breast cancer
  • Estrogen
  • Long noncoding RNA
  • RNA stability

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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