Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
Beijing Key Laboratory of Noncoding RNA, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
Sci Rep. 2016 Aug 31;6:32189. doi: 10.1038/srep32189.
The identification and characterization of long non-coding RNAs (lncRNAs) in diverse biological processes has recently developed rapidly. The large amounts of non-coding RNAs scale consistent with developmental complexity in eukaryotes, indicating that most of these transcripts may have functions in the regulation of biological processes and disorder in the organisms. In particular, Understanding of the overall biological significance of lncRNAs in cancers still remains limited. Here, we found a nuclear-retained lncRNA, termed Lnc_ASNR (apoptosis suppressing-noncoding RNA), which serves as a repressor of apoptosis. Lnc_ASNR was discovered in a set of microarray data derived from four kinds of tumor and adjacent normal tissue samples, and displayed significant up-regulation in the tumor tissues. Using an RNA-pull down assay, we found that Lnc_ASNR interacted with the protein ARE/poly (U)-binding/degradation factor 1(AUF1), which is reported to promote rapid degradation of the Bcl-2 mRNA, an inhibitor of apoptosis. Lnc_ASNR binds to AUFI in nucleus, decreasing the cytoplasmic proportion of AUF1 which targets the B-cell lymphoma-2 (Bcl-2) mRNA. Taken together, the overall effect of Lnc_ASNR expression is thus a decrease in cell apoptosis indicating that Lnc_ASNR may play a vital role in tumorigenesis and carcinogenesis.
长链非编码 RNA(lncRNA)在多种生物过程中的鉴定和特征分析最近迅速发展。大量的非编码 RNA 与真核生物的发育复杂性相一致,这表明这些转录本中的大多数可能在生物过程的调控和生物体的紊乱中具有功能。特别是,lncRNA 在癌症中的整体生物学意义的理解仍然有限。在这里,我们发现了一种核保留的 lncRNA,称为 Lnc_ASNR(凋亡抑制非编码 RNA),它作为凋亡的抑制剂。Lnc_ASNR 是在源自四种肿瘤和相邻正常组织样本的一组微阵列数据中发现的,并且在肿瘤组织中显示出明显的上调。通过 RNA 下拉测定,我们发现 Lnc_ASNR 与蛋白 ARE/多聚(U)结合/降解因子 1(AUF1)相互作用,AUF1 被报道可促进凋亡抑制剂 Bcl-2 mRNA 的快速降解。Lnc_ASNR 在核内与 AUF1 结合,减少 AUF1 的细胞质比例,AUF1 是 B 细胞淋巴瘤-2(Bcl-2)mRNA 的靶点。总之,Lnc_ASNR 表达的总体效果是细胞凋亡减少,表明 Lnc_ASNR 可能在肿瘤发生和癌变中发挥重要作用。