The pseudogene PRELID1P6 promotes glioma progression via the hnHNPH1-Akt/mTOR axis.
The pseudogene PRELID1P6 promotes glioma progression via the hnHNPH1-Akt/mTOR axis.
复制标题
假基因 PRELID1P6 通过 hnHNPH1-Akt/mTOR 轴促进神经胶质瘤进展
DOI：
10.1038/s41388-021-01854-x
复制
发表时间：
2021-07
期刊：
影响因子：
8
通讯作者：
Chen Z
中科院分区：
文献类型：
--
作者：
Xi S;Cai H;Lu J;Zhang Y;Yu Y;Chen F;Huang Q;Wang F;Chen Z
过去十年的研究表明假基因在胶质瘤中起重要作用。本研究旨在证明假基因PRELID 1 P6（pseudogene PRELI domain-containing 1 pseudogene 6）促进胶质瘤进展。使用癌症基因组图谱数据库筛选基因的异常表达。我们发现PRELID 1 P6的mRNA水平在胶质瘤中高度上调，并且与较短的生存时间相关。功能研究表明，PRELID 1 P6的敲低降低细胞增殖，球体形成和克隆形成能力，并阻止细胞周期转换在G 0/G1，而PRELID 1 P6的过表达具有相反的效果。从机制上讲，PRELID 1 P6的敲低改变了异质核核糖核蛋白H1（hnRNPH 1）从细胞核到细胞质的细胞定位，这促进了泛素介导的hnRNPH 1降解。RNA序列和基因集富集分析表明，PRELID 1 P6的敲低调节细胞凋亡信号通路。Western blotting结果显示，PRELID 1 P6通过hnRNPH 1介导的选择性剪接效应增加TRF 2的表达，并激活Akt/mTOR通路。此外，Akt抑制剂MK 2206处理逆转了PRELID 1 P6的致癌功能。PRELID 1 P6也被发现受miR-1825负调控。我们的结果表明PRELID 1 P6通过hnHNPH 1-Akt/mTOR通路促进胶质瘤进展。这些发现为PRELID 1 P6作为胶质瘤的新癌基因的重要作用提供了新的线索。
Research over the past decade has suggested important roles for pseudogenes in glioma. This study aimed to show that pseudogene PRELI domain-containing 1 pseudogene 6 (PRELID1P6) promotes glioma progression. Aberrant expression of genes was screened using The Cancer Genome Atlas database. We found that mRNA level of PRELID1P6 was highly upregulated in glioma and was associated with a shorter survival time. Functional studies showed that the knockdown of PRELID1P6 decreased cell proliferation, sphere formation, and clone formation ability and blocked the cell cycle transition at G0/G1, while overexpression of PRELID1P6 had the opposite effects. Mechanistically, knockdown of PRELID1P6 changed the cellular localization of heterogeneous nuclear ribonucleoprotein H1 (hnRNPH1) from nucleus to cytoplasm, which promoted ubiquitin-mediated degradation of hnRNPH1. RNA-sequence and gene set enrichment analysis suggested that knockdown of PRELID1P6 regulates the apoptosis signaling pathway. Western blotting showed that PRELID1P6 increased TRF2 expression by hnRNPH1-mediated alternative splicing effect and activated the Akt/mTOR pathway. Furthermore, Akt inhibitor MK2206 treatment reversed the oncogenic function of PRELID1P6. PRELID1P6 was also found to be negatively regulated by miR-1825. Our result showed that PRELID1P6 promotes glioma progression through the hnHNPH1-Akt/mTOR pathway. These findings shed new light on the important role of PRELID1P6 as a novel oncogene for glioma.
登录
查看更多内容
影响因子：
5.1
作者：
Deng, Jinmu;Chen, Song;Cheng, Yuan
通讯作者：
Cheng, Yuan
影响因子：
64.5
作者：
Rinn, John L.;Kertesz, Michael;Chang, Howard Y.
通讯作者：
Chang, Howard Y.
影响因子：
15.9
作者：
Ostrom, Quinn T.;Gittleman, Haley;Barnholtz-Sloan, Jill S.
通讯作者：
Barnholtz-Sloan, Jill S.
影响因子：
64.5
作者：
JACQ, C;MILLER, JR;BROWNLEE, GG
通讯作者：
BROWNLEE, GG
影响因子：
5.2
作者：
Hu X;Yang L;Mo YY
通讯作者：
Mo YY