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Characterization of Functionally Associated miRNAs in Glioblastoma and their Engineering into Artificial Clusters for Gene Therapy
Published on: October 4, 2019
miR-143 inhibits oncogenic traits by degrading NUAK2 in glioblastoma
Ting-Gang Fu1, Ling Wang2, Wei Li3
1Department of Neurosurgery, Yishui Central Hospital, Linyi, Shandong 276400, P.R. China.
Abstract:
Despite evidence that the crucial role of NUAK family, SNF1-like kinase, 2 [NUAK2; also known as sucrose non-fermenting 1 (SNF1)-like kinase (SNARK)], has been highlighted in cancer development and in tumor progression, to the best of our knowledge, there are no studies available to date on the role of NUAK2 in glioblastoma. Thus, in this study, in order to determine the role of NUAK2 in glioblastoma, we performed western blot analysis to detect its expression in glioma. The results demonstrated that NUAK2 expression was upregulated in glioma tissues and that its expression was associated with the advanced stages of the disease. In vitro, NUAK2 overexpression promoted the proliferation, migration and invasion of A172 glioblastoma cells, whereas the silencing of NUAK2 with a plasmid carrying shRNA targeting NUAK2 inhibited the proliferation of A172 glioblastoma cells. Moreover, NUAK2 regulated cancer stem cell (CSC)-related gene expression in the glioblastoma cells. We performed an analysis of potential microRNA (miR or miRNA) target sites using 3 commonly used prediction algorithms, miRanda, TargetScan and PicTar. All 3 algorithms predicted that miR‑143 targeted the 3'-untranslated region (3'UTR) of NUAK2. Subsequent experiments confirmed this prediction. Finally, we found that miR‑143 inhibited the proliferation, migration and invasion of the glioblastoma cells. Thus, the findings of the present study demonstrate that miR‑143 inhibits oncogenic traits by degrading NUAK2 in glioblastoma.
Insights
NUAK2 is upregulated in glioblastoma and promotes cancer growth. MicroRNA-143 targets NUAK2, inhibiting glioblastoma cell proliferation, migration, and invasion, thus acting as a tumor suppressor.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- NUAK family, SNF1-like kinase, 2 (NUAK2) is implicated in cancer development and progression.
- The specific role of NUAK2 in glioblastoma remains largely unexplored.
Purpose of the Study:
- To investigate the role of NUAK2 in glioblastoma.
- To elucidate the regulatory mechanism of NUAK2 by microRNA in glioblastoma.
Main Methods:
- Western blot analysis to detect NUAK2 expression in glioma tissues.
- In vitro experiments involving NUAK2 overexpression and silencing in A172 glioblastoma cells.
- Bioinformatic analysis and experimental validation of microRNA targeting NUAK2.
Main Results:
- NUAK2 expression is upregulated in glioma tissues and correlates with advanced disease stages.
- NUAK2 overexpression enhances glioblastoma cell proliferation, migration, and invasion.
- NUAK2 regulates cancer stem cell-related gene expression.
- MicroRNA-143 directly targets NUAK2 and inhibits glioblastoma cell oncogenic traits.
Conclusions:
- NUAK2 plays a significant oncogenic role in glioblastoma.
- MicroRNA-143 functions as a tumor suppressor in glioblastoma by targeting and degrading NUAK2.
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