Targeting the LINC00324/miR-16-5p/SEPT2 Signaling Cascade is Effective to Reverse Malignant Phenotypes in Glioblastoma

Author(s):

Bo Chen, Pengzhen Lin and Nan Li*   Pages 1535 - 1544 ( 10 )

Abstract:

Background: Long non-coding RNAs (LncRNAs) are identified as pivotal regulators and biomarkers for glioblastoma (GBM). However, the role of a novel LncRNA LINC00324 in regulating GBM progression has not been fully studied in the existing publications. </P> <P> Objective: In this study, we evidenced LINC00324 to act as an oncogene to facilitate GBM development, and the underlying mechanisms have also been uncovered. </P> <P> Methods: Clinicopathology and follow-up data of GBM patients were retrospectively studied, LINC00324 expression in clinical tissue or cell lines of GBM was measured by Real-time qPCR, and the role of LINC00324 in cell proliferation and migration was investigated by loss-of-function experiments in vitro and in vivo. The targeting genes of LINC00324 were predicted and verified by bioinformatic analysis and dual luciferase reporter gene system, respectively. </P> <P> Results: LINC00324 was found to be significantly upregulated in GBM tissues and cells in contrast to normal counterparts, and the GBM patients with high-expressed LINC00324 tended to have a worse prognosis. Further, loss-offunction experiments showed that the silencing of LINC00324 suppressed cell proliferation, colony formation and migration, and promoted cell apoptosis in GBM cells in vitro. Consistently, the in vivo experiments supported that LINC00324 ablation also restrained tumorigenesis in nude mice models. The following mechanism studies showed that LINC00324 sponged miR-16-5p to upregulate SEPT2 in a competing endogenous RNA-dependent manner, and the inhibitory effects of LINC00324 downregulation on the malignant characteristics of GBM cells were abrogated by both miR-16-5p ablation and SEPT2 overexpression. </P> <P> Conclusion: LINC00324 promotes the malignant phenotypes in GBM via targeting the miR-16-5p/SEPT2 axis, and the study provides novel biomarkers for GBM diagnosis and therapy.

Keywords:

LINC00324, glioblastoma, septin 2, miR-16-5p, proliferation, migration.

Affiliation:

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