Trait-associated loci often map to genomic regions encoding long noncoding RNAs (lncRNAs), but the role of these lncRNAs in disease etiology is largely unexplored. We show that a pair of sense/antisense lncRNA (6p22lncRNAs) encoded by CASC15 and NBAT1 located at the neuroblastoma (NB) risk-associated 6p22.3 locus are tumor suppressors and show reduced expression in high-risk NBs. Loss of functional synergy between 6p22lncRNAs results in an undifferentiated state that is maintained by a gene-regulatory network, including SOX9 located on 17q, a region frequently gained in NB. 6p22lncRNAs regulate SOX9 expression by controlling CHD7 stability via modulating the cellular localization of USP36, encoded by another 17q gene. This regulatory nexus between 6p22.3 and 17q regions may lead to potential NB treatment strategies.

中文翻译：

---

基因座6p22.3编码的有义反义lncRNA对通过USP36-CHD7-SOX9调节轴确定神经母细胞瘤的易感性。

与性状相关的基因座通常定位于编码长的非编码RNA（lncRNA）的基因组区域，但是这些lncRNA在疾病病因中的作用在很大程度上尚待探索。我们显示由位于神经母细胞瘤（NB）风险相关的6p22.3基因座的CASC15和NBAT1编码的一对有义/反义lncRNA（6p22lncRNAs）是肿瘤抑制因子，并在高风险的NBs中显示减少的表达。6p22lncRNA之间功能性协同作用的丧失导致未分化状态，该状态由基因调节网络维持，包括位于17q（位于NB中经常获得的区域）上的SOX9。6p22lncRNA通过调节CHP7的稳定性来调节SOX9的表达，该稳定性是通过调节USP36的细胞定位（由另一个17q基因编码）来实现的。6p22.3和17q区域之间的这种调节联系可能会导致潜在的NB治疗策略。