LncRNA DLGAP1‐AS1 accelerates glioblastoma cell proliferation through targeting miR‐515‐5p/ROCK1/NFE2L1 axis and activating Wnt signaling pathway

Abstract

Introduction: Glioblastoma (GBM), the primary malignant tumor in the central nervous system, features high aggressiveness and mortality. Long noncoding RNAs (lncRNAs) can exert the crucial function in regulating various human diseases, including GBM.However, the function and mechanism of lncRNA DLGAP1 antisense RNA 1 (DLGAP1-AS1) in GBM remain still unknown. Methods: DLGAP1-AS1 expression in GBM cells was detected by RT-qPCR. Functional assays were conducted to determine GBM cell proliferation and apoptosis. RIP, RNA pull down, and luciferase reporter assay were applied for measuring the interplay of DLGAP1-AS1 with other RNAs. Results: DLGAP1-AS1 was distinctly upregulated in GBM cells. DLGAP1-AS1 depletion inhibited cell proliferation, but induced apoptosis. MiR-515-5p could be sponged by DLGAP1-AS1 in GBM cells and to repress cell proliferation in GBM. Further, Rho-associated coiled-coil containing protein kinase 1 (ROCK1) and Nuclear factor erythroid-2 like 1 (NFE2L1) were confirmed as the target gene of miR-515-5p. Wnt signaling pathway could be activated by DLGAP1-AS1 via regulating ROCK1 and NFE2L1 expression. Rescue assays proved that overexpression of both ROCK1 and NFE2L1 could totally reverse the inhibitory effect of silencing DLGAP1-AS1 on GBM cell proliferation. Conclusion: LncRNA DLGAP1-AS1 accelerated cell proliferation in GBM via targeting miR-515-5p/ROCK1/NFE2L1 axis and activating Wnt signaling pathway.

A Novel Aging-Related Prognostic lncRNA Signature Correlated with Immune Cell Infiltration and Response to Immunotherapy in Breast Cancer

“…However, no reports explored the role of PRR34-AS1 in BC. According to a recent study, DLGAP1-AS1 may activate the Wnt signaling pathway to speed up the proliferation of glioblastoma and hepatocellular cancer [40,41]. However, the relationship between BC and DLGAP1-AS1 has not been pointed out.…”

circSMARCA5 Is an Upstream Regulator of the Expression of miR-126-3p, miR-515-5p, and Their mRNA Targets, Insulin-like Growth Factor Binding Protein 2 (IGFBP2) and NRAS Proto-Oncogene, GTPase (NRAS) in Glioblastoma

“…MiR-126-3p can be also carried in biological fluids through EVs [ 95 , 96 ]: it would be interesting to investigate if and how the delivery of this molecule to cells at different sites from the bulk tumor play a role in the cancer progression and resistance to the current therapies. MiR-515-5p and its target NRAS are also known to be involved in GBM progression by regulating cell migration, growth [ 53 , 54 , 55 , 56 , 97 ], and angiogenesis [ 98 , 99 ]. In an attempt to find a link between the upstream regulator circSMARCA5 and the downstream-regulated intronic miRNAs 126-3p and 515-5p, we also searched for RBPs that may commonly bind and, potentially, regulate pre-miR-126 and pre-miR-515 processing.…”

“…The following supporting information can be downloaded at: . References [ 47 , 53 , 54 , 55 , 56 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 ] are cited in the supplementary materials.…”

Unravelling the role of NFE2L1 in stress responses and related diseases

“…NFE2L1 exhibits broad expression across various tissues and is subject to regulation by multiple factors . Wang et al discovered that LncRNA DLGAP1-AS1 sponges miR-515-5p to block the expression of NFE2L1 and accelerate glioblastoma cell proliferation [ 58 ]. In 2014, Zhang et al provided evidence of NFE2L1 transcriptional activation through the mTORC1/SREBP1/NFE2L1 axis [ 57 ].…”