Oncogene, 2019-06, Vol.38 (24), p.4820-4834
2019
Details
- Autor(en) / Beteiligte
- Titel
- MicroRNA-1205, encoded on chromosome 8q24, targets EGLN3 to induce cell growth and contributes to risk of castration-resistant prostate cancer
- Ist Teil von
- Oncogene, 2019-06, Vol.38 (24), p.4820-4834
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2019
- Link zum Volltext
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- The chromosome 8q24.21 locus, which contains the proto-oncogene c-MYC, long non-coding RNA PVT1, and microRNAs (miRs), is the most commonly amplified region in human prostate cancer. A long-range interaction of genetic variants with c-MYC or long non-coding PVT1 at this locus contributes to the genetic risk of prostate cancer. At this locus is a cluster of genes for six miRs (miR-1204, -1205, -1206, -1207-3p, -1207-5p, and -1208), but their functional role remains elusive. Here the copy numbers and expression levels of miRs-1204-1208 were investigated using quantitative PCR for prostate cancer cell lines and primary tumors. The data revealed that copy numbers and expression of miR-1205 were increased in both castration-resistant prostate cancer cell lines and in primary tumors. In castration-resistant prostate cancer specimens, the copy number at the miR-1205 locus correlated with the expression of miR-1205. Furthermore, functional analysis with an miR-1205 mimic, an miR-1205 inhibitor, and CRISPR/Cas9 knockout revealed that, in human prostate cancer cells, miR-1205 promoted cell proliferation and cell cycle progression and inhibited hydrogen peroxide-induced apoptosis. In these cells, miR-1205 downregulated the expression of the Egl-9 family hypoxia inducible factor 3(EGLN3) gene and targeted a site in its 3'-untranslated region to downregulate its transcriptional activity. Thus, by targeting EGLN3, miR-1205 has an oncogenic role and may contribute to the genetic risk of castration-resistant prostate cancer.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0950-9232eISSN: 1476-5594DOI: 10.1038/s41388-019-0760-3Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6565506
- Format
- –
- Schlagworte
- Adenocarcinoma - genetics, Adenocarcinoma - pathology, Aged, Aged, 80 and over, Animals, Apoptosis, c-Myc protein, Castration, Cell cycle, Cell growth, Cell proliferation, Cell Proliferation - genetics, Chromosome 8, Chromosomes, Human, Pair 8 - genetics, Copy number, CRISPR, Gene Expression Regulation, Neoplastic, Genetic aspects, Genetic diversity, Genetic Predisposition to Disease, Health aspects, Health risk assessment, Humans, Hydrogen peroxide, Hypoxia, Hypoxia-Inducible Factor-Proline Dioxygenases - genetics, Male, Mice, Mice, Inbred BALB C, Mice, Nude, MicroRNA, MicroRNAs - genetics, MicroRNAs - physiology, Middle Aged, miRNA, Myc protein, Non-coding RNA, PC-3 Cells, Physiological aspects, Prostate cancer, Prostatic Neoplasms, Castration-Resistant - genetics, Prostatic Neoplasms, Castration-Resistant - pathology, Risk Factors, Transcription, Transcription factors, Tumor cell lines, Tumor Cells, Cultured, Tumors