m6A-Mediated Upregulation of LINC01578 Promotes the Progression of Glioma by Modulating the miR-6893-3p/TRIM14 Axis

Social Science Research Network(2022)

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摘要
Background Long noncoding RNAs (lncRNAs) play crucial roles in tumor progression and are dysregulated in glioma. However, the functional roles of lncRNAs in glioma remain largely unknown. Methods Using the TCGA and GEPIA2 databases, the overexpression of LINC01578 in glioma tissues was determined and further validated in glioma cell lines. The effects of LINC01578 on proliferation, migration, and invasion in glioma were detected by in vitro and in vivo experiments. RNA immunoprecipitation (RIP), dual luciferase reporter, RNA FISH, and RNA sequencing assays were carried out to elucidate the underlying molecular mechanisms regulated by LINC01578 in glioma. RIP and RT-qPCR was used to analyze the regulatory effect of N6-methyladenosine (m6A) on aberrantly expressed LINC01578. Results Highly expressed LINC01578 was identified in glioma tissues and was associated with poor prognosis in glioma patients. Functional assays showed that LINC01578 regulates glioma growth and metastasis in vitro and in vivo. Mechanistically, LINC01578 sponged miR-6893-3p to upregulate TRIM14 expression, thereby facilitating glioma progression. Furthermore, LINC01578 was upregulated in response to N6-methyladenosine modification, which was attributed to METTL3/YTHDF1-mediated RNA transcripts. Conclusion Our results reveal a novel m6A/LINC01578/miR-6893-3p/TRIM14 pathway for glioma progression and suggest LINC01578 as a novel prognostic indicator and therapeutic target for glioma.
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关键词
glioma,linc01578,a-mediated
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