Abstract
Glioblastoma multiforme (GBM) is a life-threatening brain tumor. This study aimed to identify potential targets of the long noncoding RNA (lncRNA) HULC that promoted the progression of GBM. Two U87 cell lines were constructed: HULC-siRNA and negative control (NC). Quantitative real-time PCR (qRT-PCR) was performed to validate the transfection efficiency of HULC silencing vector. Mass spectrometry (MS) was used to generate proteomic profiles for the two cell lines. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to distinguish HULC-related genes and pathway mapping. Colony formation, Transwell, and wound-healing assays were used to investigate the functional effects of HULC knockdown on GBM. We identified 112 up-regulated proteins and 24 down-regulated proteins from a total of 4360 quantified proteins. GO enrichment illustrated that these proteins were mainly involved in organelle structure, catalysis, cell movement, and material metabolism. KEGG pathway analysis indicated that some of these proteins were significantly enriched in tight junction, metabolic pathways, and arachidonic acid metabolism. In vitro experiments demonstrated that HULC knockdown inhibited GBM cell proliferation, invasion, and migration. Our KEGG analyses revealed that PLA2G4A was a shared protein in several enriched pathways. HULC silencing significantly down-regulated the expression of PLA2G4A. Knockdown of HULC changed the proteomic characteristics of GBM and altered the behaviors of GBM cells. Specifically, we identified PLA2G4A as an HULC target in GBM. This study provides a new perspective on the mechanisms and potential drug targets of GBM treatment.
Highlights
Glioblastoma multiforme (GBM) is a life-threatening brain tumor
Our results indicate that HULC knockdown alters the protein profile of GBM cells, which likely contributed to tumor pathogenesis
The Gene Ontology (GO) findings were unexpected in that we identified some up-regulated proteins in cell activity, such as actin filament bundles and actin binding after HULC knockdown, that indicate that HULC suppression can promote tumor migration and invasion, which contradicts our functional results
Summary
This study aimed to identify potential targets of the long noncoding RNA (lncRNA) HULC that promoted the progression of GBM. We identified PLA2G4A as an HULC target in GBM. This study provides a new perspective on the mechanisms and potential drug targets of GBM treatment. The standard treatment for GBM includes surgery, radiotherapy, and chemotherapy since targeted therapy performs poorly. Even with treatment, GBM patients have a poor prognosis. There is an urgent need to investigate the underlying pathology of GBM to identify suitable biomarkers that can facilitate early detection and diagnosis, as well as further improve treatment and prognosis. Proteomics has recently been widely used to identify new tumor b iomarkers[13,14,15].
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