Abstract
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.
Highlights
Glioblastoma (GBM) is an aggressive tumour derived from central nervous system and characterized by high recurrence rate.[1]
Extensive reports have elucidated that long non-coding RNAs (lncRNAs) undergo the main responsibility for triggering the dysregulation of various cancers
The current study manifested that PXN antisense RNA 1 (PXN-AS1) was highly overexpressed in GBM cells, and downregulated PXN-AS1 hampered cell proliferation and enhanced cell apoptosis in GBM
Summary
Glioblastoma (GBM) is an aggressive tumour derived from central nervous system and characterized by high recurrence rate.[1]. Long non-coding RNAs (lncRNAs) are one type of transcripts whose length are more than 200 nucleotides and have restriction in the ability of protein-coding.[5]. LncRNA LINC00978 functioned as a diagnostic biomarker and promotes cancer growth in gastric cancer.[11]. LncRNA FOXP4-AS1 acts as a prognostic factor in colorectal cancer and modulates colorectal cancer cell proliferation and apoptosis.[12]. LncRNA HOTAIRM1 was overexpressed in GBM and promotes cell invasion and tumour growth via up-regulating HOXA1.14 LncRNA PXN antisense RNA 1 (PXN-AS1) was reported to be down-regulated in pancreatic cancer cells and suppressed cancer progression.[15]. We explored the biological function and molecular mechanism of PXN-AS1 in GBM. SOX9-activated PXN-AS1 promoted the GBM progression by epigenetically silencing DKK1 and thereby activated Wnt/β-catenin pathway. Cell proliferation was observed using a high-power microscope and photographed on MetaXpress software (Molecular Devices)
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