Hoffmann Michèle J, Dehn Judith, Droop Johanna, Niegisch Günter, Niedworok Christian, Szarvas Tibor, Schulz Wolfgang A
Department of Urology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Germany; Moorenstrasse 5, Düsseldorf 40225, Germany.
Department of Urology, University of Duisburg-Essen, Hufelandstrasse 55, Essen 45147, Germany.
Noncoding RNA. 2015 Dec 17;1(3):266-284. doi: 10.3390/ncrna1030266.
The / locus at chromosome 9p21 encoding , and is a major tumor suppressor locus, constituting an important barrier for tumor growth. It is frequently inactivated in cancers, especially in urothelial carcinoma (UC). In addition to deletions and DNA hypermethylation, further epigenetic mechanisms might underlie its repression. One candidate factor is the long noncoding RNA ANRIL, which recruits Polycomb proteins (PcG) to regulate expression of target genes and . We observed ANRIL overexpression in many UC tissues and cell lines mainly resulting from upregulation of 3'-truncated isoforms. However, aberrant ANRIL expression was neither associated with repression of / genes nor with proliferation activity or senescence. We wondered whether truncated ANRIL isoforms exhibit altered properties resulting in loss of function . We excluded delocalization and performed RNA immunoprecipitation demonstrating interaction between full length or truncated ANRIL and PcG protein CBX7, but not SUZ12 of PRC2. Our data indicate that ANRIL in UC cells may not interact with PRC2, which is central for initializing gene repression. Thus, tissue-specific binding activities between ANRIL and PcG proteins may determine the regulatory function of ANRIL. In conclusion, ANRIL does not play a major role in repression of the / locus in UC.
位于9号染色体p21区域、编码 、 和 的基因座是一个主要的肿瘤抑制基因座，是肿瘤生长的重要屏障。它在癌症中经常失活，尤其是在尿路上皮癌（UC）中。除了缺失和DNA高甲基化外，其他表观遗传机制可能是其受到抑制的基础。一个候选因素是长链非编码RNA ANRIL，它招募多梳蛋白（PcG）来调节靶基因 和 的表达。我们观察到许多UC组织和细胞系中ANRIL过表达，主要是由于3'端截短异构体的上调。然而，异常的ANRIL表达既与 / 基因的抑制无关，也与增殖活性或衰老无关。我们想知道截短的ANRIL异构体是否表现出功能丧失的改变特性。我们排除了定位错误，并进行了RNA免疫沉淀，结果表明全长或截短的ANRIL与PcG蛋白CBX7相互作用，但不与PRC2的SUZ12相互作用。我们的数据表明，UC细胞中的ANRIL可能不与PRC2相互作用，而PRC2对启动基因抑制至关重要。因此，ANRIL与PcG蛋白之间的组织特异性结合活性可能决定ANRIL的调节功能。总之，ANRIL在UC中对 / 基因座的抑制作用不大。
