Cell type-specific reciprocal regulation of HIF1A gene expression is dependent on 5'-and 3'-UTRs
Cell type-specific reciprocal regulation of HIF1A gene expression is dependent on 5'-and 3'-UTRs
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HIF1A 基因表达的细胞类型特异性相互调节依赖于 5-和 3-UTR
DOI：
10.1016/j.bbrc.2014.04.058
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Nishioka T
中科院分区：
文献类型：
--
作者：
Yasuda M;Hatanaka T;Shirato H;Nishioka T
在本研究中，我们证明了低氧诱导因子1α(HIF1a)基因表达的相互调节是通过非翻译区依赖的机制实现的。在HIF1A5‘-UTR中发现的151个核苷酸序列足以显著上调翻译。另一方面，HIF1a的3‘-非编码区与mRNA的降解有关。在非转移性乳腺癌细胞系MCF7中，3‘-UTR依赖的下调机制占主导地位，而HIF1A的上调机制依赖于5’-UTR。然而，在转移性细胞系(MDA-MB453，U87 MG)中，5‘-UTR依赖的上调占主导地位。因此，HIF1A5‘-UTR依赖的翻译增强的优势可能是癌细胞恶性表型的关键。PTBP-1，而不是HUR，是HIF1A翻译控制的候选RNA结合蛋白。
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 theHIF1A5′-UTR is sufficient for significant translational up-regulation. On the other hand, the 3′-UTR ofHIF1Ahas 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 ofHIF1A. 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 ofHIF1Ais critical for the malignant phenotype of cancer cells. PTBP-1, but not HuR, is a candidate RNA binding protein for the translational control ofHIF1A.