Long noncoding RNA forms a growth promoting complex with HNRNPL in human glioblastoma through stabilization of ACTN4 and activation of NF-κB signaling.

Long noncoding RNA forms a growth promoting complex with HNRNPL in human glioblastoma through stabilization of ACTN4 and activation of NF-κB signaling.

Ji, Jianxiong;Xu, Ran;Ding, Kaikai;Bao, Guoqing;Zhang, Xin;Huang, Bin;Wang, Xinyu;Martinez, Aurora;Wang, Xiuying;Li, Gang;Miletic, Hrvoje;Thorsen, Frits;Bjerkvig, Rolf;Xiang, Lei;Han, Bo;Chen, Anjing;Li, Xin-Gang;Wang, Jian;
clinical cancer research : an official journal of the american association for cancer research 2019
274
ji2019longclinical

Abstract

Long noncoding RNAs (lncRNAs) have essential roles in diverse cellular processes, both in normal and diseased cell types, and thus have emerged as potential therapeutic targets. A specific member of this family, the SWI/SNF complex antagonist associated with prostate cancer 1 (), has been shown to promote aggressive prostate cancer growth by antagonizing the SWI/SNF complex and therefore serves as a biomarker for poor prognosis. Here, we investigated whether plays a potential role in the development of human glioblastoma (GBM).RNA-ISH and immunohistochemistry were performed on a tissue microarray to assess expression of and associated proteins in human gliomas. Proteins complexed with were identified using RNA pull-down and mass spectrometry. Lentiviral constructs were used for functional analysis and Results: was increased in primary GBM samples and cell lines, and knockdown of the lncRNA suppressed growth. was found to bind heterogeneous nuclear ribonucleoprotein L (HNRNPL) which stabilized the lncRNA and led to an enhanced interaction with the protein actinin alpha 4 (ACTN4). was also highly expressed in primary GBM samples and was associated with poorer overall survival in glioma patients. The -HNRNPL complex led to stabilization of ACTN4 through suppression of proteasomal degradation, which resulted in increased nuclear localization of the p65 subunit of NF-κB and activation of NF-κB signaling, a pathway associated with cancer development.Our results implicated as a driver of GBM growth as well as a potential therapeutic target in treatment of the disease.

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