SOX9‐activated PXN‐AS1 promotes the tumorigenesis of glioblastoma by EZH2‐mediated methylation of DKK1

• Published in: Journal of cellular and molecular medicine Vol. 24; no. 11; pp. 6070 - 6082
• Main Authors: Chen, Hongjin, Hou, Guoqiang, Yang, Jian, Chen, Weilin, Guo, Liemei, Mao, Qin, Ge, Jianwei, Zhang, Xiaohua
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.06.2020; John Wiley and Sons Inc
• Subjects: Animals; Antibodies; Apoptosis; Apoptosis - genetics; Base Sequence; Binding sites; Biomarkers; Brain cancer; Brain Neoplasms - genetics; Brain Neoplasms - pathology; Carcinogenesis - genetics; Carcinogenesis - pathology; Catenin; Cell growth; Cell Line, Tumor; Cell proliferation; Cell Proliferation - genetics; Colorectal cancer; Disease Progression; DKK1; Dkk1 protein; Enhancer of Zeste Homolog 2 Protein - metabolism; Epigenesis, Genetic; EZH2; Flow cytometry; Gene expression; Gene Expression Regulation, Neoplastic; Gene Silencing; Glioblastoma; Glioblastoma - genetics; Glioblastoma - pathology; Humans; Intercellular Signaling Peptides and Proteins - metabolism; Laboratory animals; Male; Methylation; Mice, Inbred BALB C; Non-coding RNA; Original; Pancreatic cancer; Plasmids; Promoter Regions, Genetic - genetics; Proteins; PXN‐AS1; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Sox9 protein; SOX9 Transcription Factor - metabolism; Tumorigenesis; Tumors; WNT pathway; Wnt protein; Wnt Signaling Pathway - genetics; WNT pathway; glioblastoma; PXN-AS1; DKK1; EZH2
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.15189

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.