Cell type-specific reciprocal regulation of HIF1A gene expression is dependent on 5′- and 3′-UTRs

被引:13
作者
Yasuda, Motoaki [1 ]
Hatanaka, Tomoyuki [1 ]
Shirato, Hiroki [2 ]
Nishioka, Takeshi [3 ]
机构
[1] Hokkaido Univ, Grad Sch Dent Med, Dept Oral Pathobiol, Kita Ku, Sapporo, Hokkaido 0608586, Japan
[2] Hokkaido Univ, Sch Med, Dept Radiat Med, Sapporo, Hokkaido 0608638, Japan
[3] Hokkaido Univ, Grad Sch Hlth Sci, Dept Biomed Sci & Engn, Kita Ku, Sapporo, Hokkaido 0600812, Japan
关键词
Hypoxia; HIF-1; alpha; UTR; Translation; Transcription; INFLAMMATORY BREAST-CANCER; HYPOXIA-INDUCIBLE FACTORS; HIF-1-ALPHA; BINDING; TRANSLATION; TWIST; RNA; PROGRESSION; INITIATION; HUR;
D O I
10.1016/j.bbrc.2014.04.058
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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. (C) 2014 Elsevier Inc. All rights reserved.
引用
收藏
页码:638 / 643
页数:6
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