USP30-AS1 促进胶质母细胞瘤细胞中线粒体的质量控制。

USP30-AS1 contributes to mitochondrial quality control in glioblastoma cells.

机构信息

State Key Laboratory of Chemical Oncogenesis, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, 518055, China; Open FIESTA Center, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, 518055, China.

Department of Neurology, Wuhan Hankou Hospital, Wuhan, 430010, China.

出版信息

Biochem Biophys Res Commun. 2021 Dec 3;581:31-37. doi: 10.1016/j.bbrc.2021.10.006. Epub 2021 Oct 9.

DOI:10.1016/j.bbrc.2021.10.006

PMID:34653676

Abstract

Glioblastoma is the most serious type of brain cancer with poor prognosis. Here, using the publicly available glioma database, we identified that USP30-AS1, an antisense lncRNA locating on the opposite strand of USP30 locus, is upregulated in human gliomas, particularly in high grade glioma. High level of USP30-AS1 is correlated with poor survival in both primary and recurrent glioma patients. USP30-AS1 regulates mitochondrial homeostasis and mitophagy in glioblastoma cells. Knockdown of USP30-AS1 decreases mitochondrial protein expression and mitochondrial mass, promotes mitochondrial uncoupler-induced mitophagy. However, USP30-AS1 does not regulate USP30 expression in a cis-regulatory manner. In summary, this study proposed that USP30-AS1 may serve as a valuable prognostic marker for gliomas. USP3-AS1 is a negative regulator of mitophagy and the regulatory effect is USP30-independent. USP30-AS1 mediated repression of mitophagy may contribute to the loss of mitochondrial homeostasis and tumor development in glioma.

摘要

胶质母细胞瘤是预后最差的一种脑癌。在这里，我们使用公开的神经胶质瘤数据库，鉴定出 USP30-AS1，一个位于 USP30 基因座反义链上的反义长非编码 RNA，在人类神经胶质瘤中上调，特别是在高级别神经胶质瘤中。USP30-AS1 的高水平与原发性和复发性神经胶质瘤患者的不良生存相关。USP30-AS1 调节胶质母细胞瘤细胞中线粒体的动态平衡和自噬。USP30-AS1 的敲低降低了线粒体蛋白的表达和线粒体的质量，促进了线粒体解偶联剂诱导的自噬。然而，USP30-AS1 并没有以顺式调控的方式调节 USP30 的表达。总之，本研究提出 USP30-AS1 可能是神经胶质瘤的一个有价值的预后标志物。USP3-AS1 是自噬的负调节剂，其调节作用不依赖于 USP30。USP30-AS1 介导的自噬抑制可能导致线粒体动态平衡的丧失和神经胶质瘤的肿瘤发展。