Abstract
Aim
Accumulating evidence suggests that lncRNAs are potential biomarkers and key regulators of tumor development and progression. However, the precise function of most lncRNAs in glioma remains unknown. In this study, we explored the role of long intergenic non-protein coding RNA 1018 (LINC01018) in human glioma.
Methods
Expression levels of LINC01018 and miR-182-5p in clinical glioma tissues and cell lines were detected by quantitative real-time PCR (qRT-PCR). Cell proliferation, migration, and invasion were determined by Cell Counting Kit-8 (CCK-8) assay and Transwell assay. Epithelial-mesenchymal transition (EMT) related proteins were measured by Western blotting. Direct relationship between LINC01018 and miR-182-5p was tested by dual-luciferase reporter assay, RNA immunoprecipitation assay (RIP), and rescue assays. Lastly, bioinformatics analyses were conducted to predict the downstream factors of LINC01018/miR-182-5p axis in glioma.
Results
LINC01018 was significantly down-regulated in glioma tissues and cell lines. Overexpression of LINC01018 dramatically inhibited cell proliferation, migration, and invasion and reverse EMT process in glioma. LINC01018 directly target to miR-182-5p. Forced up-regulation of miR-182-5p reversed the inhibitory effects on proliferative and metastatic abilities of glioma cells with LINC01018 overexpression. Lastly, the bioinformatics analyses revealed that LINC01018/miR-182-5p axis mediated a cluster of downstream genes (ADRA2C, RAB6B, RAB27B, RAPGEF5, STEAP2, TAGLN3, and UNC13C), which were potential key factors in the development of glioma.
Conclusion
LINC01018 inhibits cell proliferation and metastasis in human glioma by targeting miR-182-5p, and should be considered as a potential therapeutic target in this cancer.
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Data availability
The data used to support the findings of this study are available from the corresponding author upon request.
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The authors thank for the financial supports from Youth Program of National Natural Science Foundation of China (Grant No. 81902846) and Guangzhou Science and Technology Project (Grant No. 201707010380).
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Hu Su, Zhao Hailin and Luo Dongdong wrote the paper; Yin Jiang, Huang Shuncheng and Zhang Shun conceived the experiments; Li Dan and Peng Biao analyzed the data; Hu Su, Zhao Hailin and Luo Dongdong collected and provided the sample for this study. All authors have read and approved the final submitted manuscript.
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Su, H., Hailin, Z., Dongdong, L. et al. Long non-coding RNA LINC01018 inhibits human glioma cell proliferation and metastasis by directly targeting miRNA-182-5p. J Neurooncol 160, 67–78 (2022). https://doi.org/10.1007/s11060-022-04113-5
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DOI: https://doi.org/10.1007/s11060-022-04113-5