期刊
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
卷 23, 期 8, 页码 5048-5062出版社
WILEY
DOI: 10.1111/jcmm.14362
关键词
glioma; LMX1A; long non-coding RNAs; miR-499a-5p; NLRC5; SCAMP1
资金
- Natural Science Foundation of China [81872073, 81872503, 81672511, 81573010]
- Liaoning Science and Technology Plan Project [2017225020, 2015225007]
- Project of Key Laboratory of Neuro-oncology in Liaoning Province [112-2400017005]
- Special developmental project by central government of Liaoning Province [2017011553-301]
- Outstanding scientific fund of Shengjing hospital [201304]
Dysregulation of long non-coding RNAs (lncRNAs) confirm that it plays a crucial role in tumourigenesis and malignant progression of glioma. The present study demonstrated that LncRNA secretory carrier membrane protein 1 (SCAMP1) was up-regulated and functioned as an oncogene in glioma cells. In addition, miR-499a-5p was down-regulated meanwhile exerted tumour-suppressive function in glioma cells. Subsequently, inhibition of SCAMP1 significantly restrained the cell proliferation, migration and invasion, as well as promoted apoptosis by acting as a molecular sponge of miR-499a-5p. Transcription factor LIM homeobox transcription factor 1, alpha (LMX1A) was overexpressed in glioma tissues and cells. Moreover, miR-499a-5p targeted LMX1A 3'-UTR in a sequence-specific manner. Hence, down-regulation of SCAMP1 remarkably reduced the expression level of LMX1A, indicating that LMX1A participated in miR-499a-5p-induced tumour-suppressive effects on glioma cells. Furthermore, knockdown of LMX1A decreased NLR family, CARD domain containing 5 (NLRC5) mRNA and protein expression levels through directly binding to the NLRC5 promoter region. Down-regulation of NLRC5 obviously inhibited malignant biological behaviours of glioma cells through attenuating the activity of Wnt/beta-catenin signalling pathway. In conclusion, our study clarifies that SCAMP1/miR-499a-5p/LMX1A/NLRC5 axis plays a critical role in modulating malignant progression of glioma cells, which provide a novel therapeutic strategy for glioma treatment.
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