Pilyugin Maxim, Irminger-Finger Irmgard
Department of Gynecology and Obstetrics and Department of Medical Genetics and Laboratory Medicine, University Hospitals of Geneva, 2, Chemin du Petit Bel Air, 1225 Geneva, GE, Switzerland.
Department of Gynecology and Obstetrics and Department of Medical Genetics and Laboratory Medicine, University Hospitals of Geneva, 2, Chemin du Petit Bel Air, 1225 Geneva, GE, Switzerland.
Int J Biochem Cell Biol. 2014 Sep;54:356-67. doi: 10.1016/j.biocel.2014.06.018. Epub 2014 Jul 5.
Long non-coding RNAs (lncRNAs) are ubiquitously expressed RNA molecules of more than 200 nucleotides without substantial ORFs. LncRNAs could act as epigenetic regulators of gene expression affecting transcription, mRNA stability and transport, and translation, although, precise functions have been attributed to only few of them. Competing endogenous RNAs (ceRNAs) represent one recently emerged type of functional lncRNAs that share microRNA recognition sequences with mRNAs and may compete for microRNA binding and thus affect regulation and function of target mRNAs. We studied the epigenetic regulation of the BARD1 gene. The BARD1 protein acts as tumor suppressor with BRCA1. In cancer, mRNAs encoding the tumor suppressor full length BARD1 are often down-regulated while the expression of oncogenic truncated isoforms is boosted. We found that the BARD1 3'UTR is almost 3000nt long and harbors a large number of microRNA binding elements. In addition we discovered a novel lncRNA, BARD1 9'L, which is transcribed from an alternative promoter in intron 9 of the BARD1 gene and shares part of the 3'UTR with the protein coding BARD1 mRNAs. We demonstrate with the example of two microRNAs, miR-203 and miR-101, that they down-regulate the expression of FL BARD1 and cancer-associated BARD1 mRNAs, and that BARD1 9'L counteracts the effect of miR-203 and miR-101, As BARD1 9'L is abnormally over-expressed in human cancers, we suggest it might be a tumor promoting factor and treatment target. This article is part of a Directed Issue entitled: The Non-coding RNA Revolution.
长链非编码RNA（lncRNAs）是普遍表达的RNA分子，由超过200个核苷酸组成，没有大量的开放阅读框。lncRNAs可作为基因表达的表观遗传调节因子，影响转录、mRNA稳定性和转运以及翻译，尽管只有少数lncRNAs的精确功能已被确定。竞争性内源性RNA（ceRNAs）是最近出现的一种功能性lncRNAs，它们与mRNA共享微小RNA识别序列，并可能竞争微小RNA结合，从而影响靶mRNA的调控和功能。我们研究了BARD1基因的表观遗传调控。BARD1蛋白与BRCA1一起作为肿瘤抑制因子。在癌症中，编码肿瘤抑制因子全长BARD1的mRNA常常下调，而致癌性截短异构体的表达则增强。我们发现BARD1的3'UTR几乎有3000nt长，并且含有大量的微小RNA结合元件。此外，我们发现了一种新的lncRNA，BARD1 9'L，它从BARD1基因内含子9中的一个替代启动子转录而来，并与编码BARD1蛋白的mRNA共享部分3'UTR。我们以两种微小RNA，miR-203和miR-101为例，证明它们下调FL BARD1和癌症相关BARD1 mRNA的表达，并且BARD1 9'L抵消了miR-203和miR-101的作用。由于BARD1 9'L在人类癌症中异常过度表达，我们认为它可能是一种肿瘤促进因子和治疗靶点。本文是名为：非编码RNA革命的定向问题的一部分。
