scholarly journals Long non-coding RNA (lncRNA): A potential therapeutic target in acute lung injury

Author(s):  
Almaz Zaki ◽  
M Shadab Ali ◽  
Vijay Hadda ◽  
Syed Mansoor Ali ◽  
Anita Chopra ◽  
...  
Oncotarget ◽  
2014 ◽  
Vol 5 (3) ◽  
pp. 764-774 ◽  
Author(s):  
Francesco Crea ◽  
Akira Watahiki ◽  
Luca Quagliata ◽  
Hui Xue ◽  
Larissa Pikor ◽  
...  

2019 ◽  
Vol 44 (1) ◽  
pp. 317-326 ◽  
Author(s):  
Wei‐Jun Liang ◽  
Xiao‐Yuan Zeng ◽  
Sha‐Li Jiang ◽  
Hong‐Yi Tan ◽  
Mu‐Yun Yan ◽  
...  

2021 ◽  
Vol 25 (4) ◽  
pp. 1851-1866
Author(s):  
Caiming Xu ◽  
Yalan Luo ◽  
Michael Ntim ◽  
Weili Quan ◽  
Zhaoxia Li ◽  
...  

2020 ◽  
Author(s):  
Keisuke Katsushima ◽  
Bongyong Lee ◽  
Haritha Kunhiraman ◽  
Cuncong Zhong ◽  
Rabi Murath ◽  
...  

AbstractBackgroundMedulloblastoma (MB) is an aggressive brain tumor that predominantly affects children. Recent high-throughput sequencing studies suggest that the non-coding RNA genome, in particular long non-coding RNAs (lncRNAs), contributes to MB sub-grouping. Here we report the identification of a novel lncRNA, lnc-HLX-2-7, as a potential molecular marker and therapeutic target in group 3 MBs.MethodsPublicly available RNA sequencing (RNA-seq) data from 175 MB patients were interrogated to identify lncRNAs that differentiate between MB subgroups. After characterizing a subset of differentially expressed lncRNAs in vitro and in vivo, the group 3-enriched lncRNA lnc-HLX2-7 was deleted by CRISPR/Cas9 in the MB cell line D425 Med. Intracranially injected tumors were further characterized by bulk and single-cell RNA-sequencing.Resultslnc-HLX-2-7 is highly upregulated in group 3 MB cell lines, patient-derived xenografts, and primary MBs compared to other MB sub-groups as assessed by qRT-PCR, RNA-seq, and RNA fluorescence in situ hybridization (FISH). Depletion of lnc-HLX-2-7 with antisense oligonucleotides or CRISPR/Cas9 significantly reduced cell proliferation and 3D colony formation and induced apoptosis. lnc-HLX-2-7-deleted D425 Med cells injected into mouse cerebella produced smaller tumors than those derived from parental cells. Pathway analysis revealed that lnc-HLX2-7 modulated oxidative phosphorylation, mitochondrial dysfunction, and sirtuin signaling pathways. The MYC oncogene regulated lnc-HLX-2-7, and the small molecule BET-bromodomain (BRD4) inhibitor JQ1 reduced lnc-HLX2-7 expression.Conclusionslnc-HLX-2-7 is oncogenic in MB and represents a promising novel molecular marker and a potential therapeutic target in group 3 MBs in children.Key pointslnc-HLX-2-7 is highly upregulated in group 3 medulloblastomas compared to other sub-groups.In vitro and in vivo studies strongly support an oncogenic role for lnc-HLX2-7 in group 3 medulloblastoma.lnc-HLX-2-7 may be a novel biomarker and a potential therapeutic target in group 3 medulloblastoma.Importance of the studyGroup 3 medulloblastomas are associated with poor clinical outcomes, are difficult to subtype clinically, and their biology is poorly understood. In an effort to address these problems, we identified a group 3-specific long non-coding RNA, lnc-HLX-2-7, in an in silico analysis of 175 medulloblastomas and confirmed its expression in group 3 medulloblastoma cell lines, patient-derived xenografts, and FFPE samples. CRISPR/Cas9 deletion and antisense oligonucleotide knockdown of lnc-HLX-2-7 significantly reduced cell growth and 3D colony formation and induced apoptosis. Deletion of lnc-HLX-2-7 in cells injected into mouse cerebellums reduced tumor growth compared to parental cells, and RNA sequencing of these tumors revealed lnc-HLX-2-7-associated modulation of cell viability and cell death signaling pathways. The oncogene MYC regulates lnc-HLX-2-7, and its expression can be controlled by the BET-bromodomain (BRD4) inhibitor JQ1. lnc-HLX-2-7 is a candidate biomarker and a potential therapeutic target in group 3 medulloblastomas in children.


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