靶向长链非编码 RNA HMMR-AS1 抑制并放射增敏胶质母细胞瘤。

Targeting Long Noncoding RNA HMMR-AS1 Suppresses and Radiosensitizes Glioblastoma.

机构信息

Department of Neurosurgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, China.

出版信息

Neoplasia. 2018 May;20(5):456-466. doi: 10.1016/j.neo.2018.02.010. Epub 2018 Mar 22.

Emergent evidences revealed that long noncoding RNAs (lncRNAs) participate in neoplastic progression. HMMR is an oncogene that is highly expressed in glioblastoma (GBM) and supports GBM growth. Whether lncRNAs regulate HMMR in GBM remains unknown. Herein, we identify that an HMMR antisense lncRNA, HMMR-AS1, is hyperexpressed in GBM cell lines and stabilizes HMMR mRNA. Knockdown of HMMR-AS1 reduces HMMR expression; inhibits cell migration, invasion, and mesenchymal phenotypes; and suppresses GBM cell growth both in vitro and in vivo. Moreover, knockdown of HMMR-AS1 radiosensitizes GBM by reducing DNA repair proteins ATM, RAD51, and BMI1. Our data demonstrate a mechanism of sense-antisense interference between HMMR and HMMR-AS1 in GBM and suggest that targeting HMMR-AS1 is a potential strategy for GBM treatment.

越来越多的证据表明，长非编码 RNA（lncRNA）参与了肿瘤的发生发展。HMMR 是一种在神经胶质瘤（GBM）中高表达的癌基因，支持 GBM 的生长。lncRNA 是否在 GBM 中调节 HMMR 尚不清楚。本文中，我们发现 HMMR 反义 lncRNA HMMR-AS1 在 GBM 细胞系中高表达，并稳定 HMMR mRNA。敲低 HMMR-AS1 可降低 HMMR 表达；抑制细胞迁移、侵袭和间充质表型；并抑制体外和体内 GBM 细胞生长。此外，敲低 HMMR-AS1 通过减少 DNA 修复蛋白 ATM、RAD51 和 BMI1 来增敏 GBM。我们的数据表明在 GBM 中 HMMR 和 HMMR-AS1 之间存在一种 sense-antisense 干扰机制，并提示靶向 HMMR-AS1 可能是治疗 GBM 的一种策略。