Abstract
Glioma is the most common malignant brain tumor and long non-coding RNAs (lncRNAs) have been reported to play an important role in the growth and angiogenesis of glioma. However, the potential mechanisms of lncRNA H19 in glioma remain unclear. In the present study, the effects of lncRNA H19 on glioma cell proliferation, migration, and angiogenesis were evaluated. The expression levels of H19, miR-342, and Wnt5a in glioma tissues and cells were detected by RT-qPCR or Western blotting. Dual luciferase reporter assay confirmed the interaction between H19, miR-342, and Wnt5a. Cell proliferation, migration, and angiogenesis were analyzed by colony formation, transwell, and tube formation assays, respectively. IHC was performed to test the angiogenesis-related factor CD31. H19 and Wnt5a expression were remarkably upregulated in glioma tissues and cells, whereas miR-342 expression was downregulated. Moreover, functional analysis confirmed that knockdown of H19 or overexpression of miR-342 suppressed glioma cell proliferation, migration, and angiogenesis in vitro. Besides, H19 was found to directly target miR-342 to promote Wnt5a expression and activate β-catenin pathway in glioma cells. Moreover, suppression of miR-342 or overexpression of Wnt5a reversed the inhibitory effect of sh-H19 on glioma growth and metastasis. Additionally, we verified that H19 promoted glioma cell proliferation, migration, and angiogenesis via miR-342/Wnt5a/β-catenin axis in vivo. H19 regulates glioma cell growth and metastasis through miR-342 to mediate Wnt5a/β-catenin signaling pathway, which provides new therapeutic targets for glioma treatment.
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Data Availability
The datasets used or analyzed during the current study are available from the corresponding author on reasonable request.
Code Availability
Not applicable.
Abbreviations
- lncRNAs:
-
Long non-coding RNAs
- miRNAs:
-
MicroRNAs
- NHA:
-
Normal human astrocytes
- HUVECs:
-
Human umbilical vein endothelial cells
- shRNA:
-
Short hairpin RNA
- IHC:
-
Immunohistochemistry
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Acknowledgements
Thanks to National Natural Science Foundation of China (Grant No. 81803582) for supporting our work.
Funding
This work was supported by National Natural Science Foundation of China (No. 81803582), Natural Science Foundation of Hunan Province for Young Scholar (No. 2020JJ5957).
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This study was designed by W-LK and QZ. Z-ZL made great contribution to the data collection of this study. HW and QZ were responsible for the data analysis and ascertained the integrity as well as accuracy of the data. QZ and W-LK prepared and approved this manuscript.
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All experiments were conducted with the approval of the Clinical Research Ethics Committee of Xiangya Hospital of Central South University.
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Zhou, Q., Liu, ZZ., Wu, H. et al. LncRNA H19 Promotes Cell Proliferation, Migration, and Angiogenesis of Glioma by Regulating Wnt5a/β-Catenin Pathway via Targeting miR-342. Cell Mol Neurobiol 42, 1065–1077 (2022). https://doi.org/10.1007/s10571-020-00995-z
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DOI: https://doi.org/10.1007/s10571-020-00995-z