PSF Promotes ER-Positive Breast Cancer Progression via Posttranscriptional Regulation of ESR1 and SCFD2
| Autor: | Yutaka Suzuki, Kuniko Horie-Inoue, Hidetaka Kawabata, Takashi Suzuki, Kazuhiro Ikeda, Satoshi Inoue, Yuichi Mitobe, Kenjiro Aogi, Kaori Iino, Ken-ichi Takayama |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Regulation of gene expression Cancer Research Gene knockdown Microarray business.industry Estrogen receptor medicine.disease medicine.disease_cause Metastasis 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Breast cancer Oncology 030220 oncology & carcinogenesis medicine Cancer research business Carcinogenesis Estrogen receptor alpha |
| Zdroj: | Cancer Research. 80:2230-2242 |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | Endocrine therapy is standard treatment for estrogen receptor (ER)-positive breast cancer, yet long-term treatment often causes acquired resistance, which results in recurrence and metastasis. Recent studies have revealed that RNA-binding proteins (RBP) are involved in tumorigenesis. Here, we demonstrate that PSF/SFPQ is an RBP that potentially predicts poor prognosis of patients with ER-positive breast cancer by posttranscriptionally regulating ERα (ESR1) mRNA expression. Strong PSF immunoreactivity correlated with shorter overall survival in patients with ER-positive breast cancer. PSF was predominantly expressed in a model of tamoxifen-resistant breast cancer cells, and depletion of PSF attenuated proliferation of cultured cells and xenografted tumors. PSF expression was significantly associated with estrogen signaling. PSF siRNA downregulated ESR1 mRNA by inhibiting nuclear export of the RNA. Integrative analyses of microarray and RNA immunoprecipitation sequencing also identified SCFD2, TRA2B, and ASPM as targets of PSF. Among the PSF targets, SCFD2 was a poor prognostic indicator of breast cancer and SCFD2 knockdown significantly suppressed breast cancer cell proliferation. Collectively, this study shows that PSF plays a pathophysiologic role in ER-positive breast cancer by posttranscriptionally regulating expression of its target genes such as ESR1 and SCFD2. Overall, PSF and SCFD2 could be potential diagnostic and therapeutic targets for primary and hormone-refractory breast cancers. Significance: This study defines oncogenic roles of RNA-binding protein PSF, which exhibits posttranscriptional regulation in ER-positive breast cancer. |
| Databáze: | OpenAIRE |
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