LncRNA WEE2-AS1 Knockdown Inhibits the Proliferation, Migration and 3 Invasion of Glioma Cells via Regulating miR-29b-2-5p/TPM3 Axis

LncRNA WEE2-AS1 敲低通过调控 miR-29b-2-5p/TPM3 轴抑制胶质瘤细胞增殖、迁移和侵袭

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作者:Zhen Jia, Zhengting Qian, Yong Tang, Xiang Li, Yan Shi, Heng Xin, Youwu Fan, Heming Wu

Abstract

Glioma is a general malignant tumor with a dismal prognosis. Long noncoding RNAs (lncRNAs) have been implicated in the initiation and processes of tumors. An investigation of the GEPIA database revealed that long noncoding RNA WEE2 antisense RNA 1 (WEE2-AS1) is upregulated in glioma tissues compared to normal brain tissues, and validation with quantitative real-time polymerase chain reaction (qRT-PCR) revealed that WEE2-AS1 expression was consistent with the database prediction. Fluorescence in situ hybridization (FISH) assays revealed that WEE2-AS1 was localized primarily in the cytoplasm. Clone formation experiment and EDU assay were used to detect cell proliferation ability, and Transwell assay was used to detect cell migration and invasion ability, Western-blot assay and immunofluorescence were used to determine TPM3 protein level. Functional experiments revealed that the downregulation of WEE2-AS1 impeded cell proliferation, migration, and invasion in glioma cell lines. Furthermore, downregulation of WEE2-AS1 suppressed tumor growth in vivo. Bioinformatics predictions and integrated experiments indicated that WEE2-AS1 promoted tropomyosin 3 (TPM3) expression by sponging miR-29b-2-5p. A dual-luciferase reporter assay was conducted to uncover the binding of WEE2-AS1 and miR-29b-2-5p and that of miR-29b-2-5p and TPM3. Additionally, a series of rescue assays showed that WEE2-AS1 promotes proliferation, migration, and invasion by targeting miR-29b-2-5p to regulate TPM3 expression. Ultimately, the results of this study indicate that WEE2-AS1 plays an oncogenic role in glioma and may promote further investigations of the diagnostic and prognostic value of WEE2-AS1 in glioma.

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