Cell type-specific reciprocal regulation of HIF1A gene expression is dependent on 5′- and 3′-UTRs |
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Authors: | Motoaki Yasuda Tomoyuki Hatanaka Hiroki Shirato Takeshi Nishioka |
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Affiliation: | 1. Department of Oral Pathobiology, Graduate School of Dental Medicine, Hokkaido University, N13 W7, Kita-ku, Sapporo 060-8586, Japan;2. Department of Radiation Medicine, Hokkaido University School of Medicine, K15 W7, Kita-ku, Sapporo 060-8638, Japan;3. Department of Biomedical Sciences and Engineering, Graduate School of Health Sciences, Hokkaido University, N12 W5, Kita-ku, Sapporo 060-0812, Japan |
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Abstract: | In the present study, we demonstrated the reciprocal regulation of hypoxia-inducible factor 1 alpha (HIF1A) gene expression via untranslated region-(UTR) dependent mechanisms. A 151 nucleotide sequence found in the HIF1A 5′-UTR is sufficient for significant translational up-regulation. On the other hand, the 3′-UTR of HIF1A has been implicated in mRNA degradation. In the non-metastatic breast cancer cell line MCF7, the 3′-UTR-dependent down-regulatory machinery predominates over the 5′-UTR-dependent up-regulation of HIF1A. However, 5′-UTR-dependent up-regulation is dominant among metastatic cell lines (MDA-MB453, U87MG). It is therefore likely that the predominance of 5′-UTR-dependent translational enhancement of HIF1A is critical for the malignant phenotype of cancer cells. PTBP-1, but not HuR, is a candidate RNA binding protein for the translational control of HIF1A. |
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Keywords: | Hypoxia HIF-1α UTR Translation Transcription |
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