期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 20, 期 15, 页码 -出版社
MDPI
DOI: 10.3390/ijms20153713
关键词
LINC01537; PDE2A; survival; energy metabolism; lung cancer
资金
- National Natural Science Foundation of China [81473040, 81673267, 81872694, 81402753, 81672303, 81602289]
- Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program [2017BT01S155]
- National Key RD Projects [2016YFC0903700]
- Guangzhou Science and Technology Program Pearl River Nova projects [201710010049]
- Guangzhou Education Bureau Major projects [1201610122]
- Yangcheng Scholar Grants [1201541589]
- Guangdong High School Young Innovative Talents Project [2015KQNCX136]
- Guangzhou Science Research Program General Projec [201707010123]
- Guangzhou Municipal Scientific Research Project [1201630073]
Many long non-coding RNAs (lncRNAs) have emerged as good biomarkers and potential therapeutic targets for various cancers. We aimed to get a detailed understanding of the lncRNA landscape that is associated with lung cancer survival. A comparative analysis between our RNA sequencing (RNA-seq) data and TCGA datasets was conducted to reveal lncRNAs with significant correlations with lung cancer survival and then the association of the most promising lncRNA was validated in a cohort of 243 lung cancer patients. Comparing RNA-seq data with TCGA ones, 84 dysregulated lncRNAs were identified in lung cancer tissues, among which 10 lncRNAs were significantly associated with lung cancer survival. LINC01537 was the most significant one (p = 2.95 x 10(-6)). Validation analysis confirmed the downregulation of LINC01537 in lung cancer. LINC01537 was observed to inhibit tumor growth and metastasis. It also increased cellular sensitivity to nilotinib. PDE2A (phosphodiesterase 2A) was further identified to be a target of LINC01537 and it was seen that LINC01537 promoted PDE2A expression via RNA-RNA interaction to stabilize PDE2A mRNA and thus echoed effects of PDE2A on energy metabolism including both Warburg effect and mitochondrial respiration. Other regulators of tumor energy metabolism were also affected by LINC01537. These results elucidate a suppressed role of LINC01537 in lung cancer development involving tumor metabolic reprogramming, and we believe that it might be a biomarker for cancer survival prediction and therapy.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据