Open AccessSOX9‐activated PXN‐AS1 promotes the tumorigenesis of glioblastoma by EZH2‐mediated methylation of DKK1
Author(s) -
Chen Hongjin,
Hou Guoqiang,
Yang Jian,
Chen Weilin,
Guo Liemei,
Mao Qin,
Ge Jianwei,
Zhang Xiaohua
Publication year - 2020
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.15189
Subject(s) - biology , wnt signaling pathway , cancer research , dkk1 , carcinogenesis , ezh2 , epigenetics , cancer , signal transduction , microbiology and biotechnology , genetics , gene
Increasing evidence has validated the essential regulation of long non‐coding RNAs (lncRNAs) in the biological process of tumours. LncRNA PXN‐AS1 has been discovered to be as a tumour suppressor in pancreatic cancer; however, its function and mechanism remain greatly unknown in glioblastoma (GBM). Our present study indicated that PXN‐AS1 was highly expressed in GBM tissues and cells. Besides, the knock‐down of PXN‐AS1 was closely associated with the inhibitory proliferation and inducing apoptosis of GBM cells. PXN‐AS1 inhibition was also found to restrain GBM tumour growth. Importantly, SOX9 functioned as a transcription factor and activated PXN‐AS1 expression, and overexpressed PXN‐AS1 rescued the inhibitory role of down‐regulated SOX9 in GBM cell growth. Subsequently, it was discovered that PXN‐AS1 activated Wnt/β‐catenin pathway. DKK1 was widely known as an inhibitor gene of Wnt/β‐catenin pathway, and its expression was negatively associated with PXN‐AS1 and SOX9. Interestingly, we found that PXN‐AS1 could recruit EZH2 to mediate the H3K27me3 level of DKK1 promoter. Restoration experiments manifested that DKK1 knock‐down counteracted PXN‐AS1 depletion‐mediated repression in GBM cell growth. All facts pointed out that PXN‐AS1 might be of importance in exploring the therapeutic strategies of GBM.