泛癌长链非编码 RNA PLANE 通过调控可变剪接程序促进癌症发生。

The pan-cancer lncRNA PLANE regulates an alternative splicing program to promote cancer pathogenesis.

机构信息

Translational Research Institute, Henan Provincial People's Hospital and People's Hospital of Zhengzhou University, Academy of Medical Science, Zhengzhou University, Henan, China.

School of Medicine and Public Health, The University of Newcastle, Callaghan, NSW, Australia.

出版信息

Nat Commun. 2021 Jun 18;12(1):3734. doi: 10.1038/s41467-021-24099-4.

Genomic amplification of the distal portion of chromosome 3q, which encodes a number of oncogenic proteins, is one of the most frequent chromosomal abnormalities in malignancy. Here we functionally characterise a non-protein product of the 3q region, the long noncoding RNA (lncRNA) PLANE, which is upregulated in diverse cancer types through copy number gain as well as E2F1-mediated transcriptional activation. PLANE forms an RNA-RNA duplex with the nuclear receptor co-repressor 2 (NCOR2) pre-mRNA at intron 45, binds to heterogeneous ribonucleoprotein M (hnRNPM) and facilitates the association of hnRNPM with the intron, thus leading to repression of the alternative splicing (AS) event generating NCOR2-202, a major protein-coding NCOR2 AS variant. This is, at least in part, responsible for PLANE-mediated promotion of cancer cell proliferation and tumorigenicity. These results uncover the function and regulation of PLANE and suggest that PLANE may constitute a therapeutic target in the pan-cancer context.

3q 染色体远端部分的基因组扩增，编码了许多致癌蛋白，是恶性肿瘤中最常见的染色体异常之一。在这里，我们对 3q 区域的一个非蛋白产物——长非编码 RNA（lncRNA）PLANE 进行了功能表征，该 RNA 通过拷贝数增加以及 E2F1 介导的转录激活，在多种癌症类型中上调。PLANE 在 45 号内含子处与核受体共抑制因子 2（NCOR2）前体 mRNA 形成 RNA-RNA 双链，与异质核糖核蛋白 M（hnRNPM）结合，并促进 hnRNPM 与内含子的结合，从而抑制产生 NCOR2-202 的选择性剪接（AS）事件，NCOR2-202 是主要的蛋白编码 NCOR2 AS 变体。这至少部分解释了 PLANE 促进癌细胞增殖和致瘤性的机制。这些结果揭示了 PLANE 的功能和调控机制，并表明 PLANE 可能成为泛癌治疗的靶点。