論文 - 詳細
| RRC ID | 81504 |
|---|---|
| 著者 | Tsuji K, Kawata H, Kamiakito T, Nakaya T, Tanaka A. |
| タイトル | RNA-binding protein 14 promotes phase separation to sustain prostate specific antigen expression under androgen deprivation in human prostate cancer. |
| ジャーナル | J Steroid Biochem Mol Biol |
| Abstract |
Castration-resistant prostate cancer (CRPC) is a big challenge in managing prostate cancer patients. The androgen receptor (AR) pathway is a major driver even in CRPC under androgen deprivation. The mechanism in maintaining of the AR pathway under androgen deprivation remains elusive. The recent discovery of biomolecular condensate, a membrane-less intracellular construct formed by liquid-liquid phase separation (LLPS), that facilitate molecular assembly, encouraged the re-screening of our previous microarray data list. We selected Rbm14 as a target molecule for further analysis because it works as a coactivator of nuclear receptors as well as it facilitates formation of biomolecular condensates via its intrinsically disordered region. GFP-tagged Rbm14 transfected into HEK293T cells formed droplet-like puncta, which diminished following treatment with 1,6-hexanediol. Droplet-like structures were also observed in immunofluorescence for endogenous RBM14 of PC-3 and DU145 cells. Luciferase assay revealed that Rbm14 enhanced androgen-responsive element (ARE)-mediated reporter activity in all conditions with or without testosterone and AR. Co-immunoprecipitation confirmed the Rbm14-AR interaction. Long non-coding RNAs, including NEAT1, SRA1, and HOTAIR, were also interacted with Rbm14. Small interfering RNAs of NEAT1 reduced ARE-mediated reporter activity, while transfection of SRA1 and HOTAIR enhance the reporter activity. Treatment with 1,6-hexanediol as well as transfection with a dominant-negative splice variant of Rbm14 reduced expression of prostate specific antigen (PSA), a prototype of androgen-regulated gene, in LNCaP, PC-3, and DU145 cells under androgen deprivation. Immunohistochemically, RBM14 expression was substantially upregulated in prostate cancer tissues after androgen deprivation therapy than in untreated tumors. In conclusion, RBM14 is a novel factor involved in maintenance of PSA expression via phase separation under androgen deprivation in prostate cancer. |
| 巻・号 | 235 |
| ページ | 106407 |
| 公開日 | 2023-12-1 |
| DOI | 10.1016/j.jsbmb.2023.106407 |
| PII | S0960-0760(23)00162-0 |
| PMID | 37806532 |
| MeSH | Androgens* / metabolism Cell Line, Tumor HEK293 Cells Humans Male Prostate-Specific Antigen* / metabolism Prostatic Neoplasms* / drug therapy Prostatic Neoplasms* / genetics Prostatic Neoplasms* / metabolism Prostatic Neoplasms, Castration-Resistant* / pathology RNA-Binding Proteins* / genetics Receptors, Androgen / metabolism |
| IF | 3.813 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 遺伝子材料 | pAc-GFPN1 mouse dominant-negative Rbm14 (RDB20312) C-flag mRbm14 (RDB20314) pAc-GFPN1 Rbm14 (RDB20318) pGL-3 hPSA promoter (RDB20330) C-flag mouse dominant-negative Rbm14 (RDB20331) |