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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
microRNA-1296 Inhibits Glioma Cell Growth by Targeting ABL2
Gaolian Zhang1, Meng Xia1, Jianhui Guo1
1Department of Neurosurgery, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning, People's Republic of China.
Abstract:
Aberrant expression of microRNAs (miRNAs) has been reported to play a role in tumorigenesis. Dysfunction of miR-1296 was found in a variety of cancers, however, the function of miR-1296 in the progression of glioma remains largely understood. Here, our results showed that miR-1296 was significantly down-regulated in glioma tissues and cell lines. Decreased expression of miR-1296 was associated with the tumor size, WHO grade and karnofsky performance scale (KPS) of glioma patients. Low expression of miR-1296 was significantly correlated with the shorter 5-year overall survival of glioma patients. Overexpression of miR-1296 inhibited the proliferation, colony formation, migration and induced apoptosis of glioma cells. MiR-1296 was found to bind the 3'-untranslated region (UTR) of ABL proto-oncogene 2 (ABL2) and subsequently repressed both the mRNA and protein expression of ABL2. ABL2 was overexpressed in glioma tissues and inversely correlated with that of miR-1296. Ectopic expressed ABL2 could reverse the inhibitory effects of miR-1296 on glioma cell proliferation. Our results illustrated the novel tumor-suppressive function of miR-1296 in glioma via repressing ABL2, suggesting a potential application of miR-1296 in the treatment of glioma.
Insights
MicroRNA-1296 (miR-1296) acts as a tumor suppressor in glioma by inhibiting cell growth and promoting apoptosis. Its down-regulation is linked to poorer patient outcomes, suggesting miR-1296 as a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Aberrant microRNA (miRNA) expression is implicated in cancer development.
- The specific role of miR-1296 in glioma progression is not well understood.
- Dysfunction of miR-1296 is observed in various cancers.
Purpose of the Study:
- To investigate the function of miR-1296 in glioma.
- To determine the relationship between miR-1296 expression and clinicopathological features of glioma patients.
- To identify the molecular mechanism underlying miR-1296's role in glioma.
Main Methods:
- Quantitative real-time PCR to measure miR-1296 and ABL2 expression in glioma tissues and cell lines.
- Analysis of correlation between miR-1296 expression and patient survival, tumor size, WHO grade, and Karnofsky performance scale (KPS).
- In vitro assays (proliferation, colony formation, migration, apoptosis) to assess the functional impact of miR-1296 and ABL2.
- Luciferase reporter assay to confirm the binding of miR-1296 to the 3'-untranslated region (UTR) of ABL2.
Main Results:
- miR-1296 was significantly down-regulated in glioma tissues and cell lines.
- Low miR-1296 expression correlated with larger tumor size, higher WHO grade, lower KPS, and shorter 5-year overall survival.
- Overexpression of miR-1296 suppressed glioma cell proliferation, colony formation, and migration, while inducing apoptosis.
- miR-1296 directly targets and represses ABL proto-oncogene 2 (ABL2) expression.
- ABL2 was overexpressed in glioma and its ectopic expression reversed the inhibitory effects of miR-1296.
Conclusions:
- miR-1296 functions as a tumor suppressor in glioma by inhibiting cell proliferation and migration.
- The tumor-suppressive role of miR-1296 is mediated through the repression of ABL2.
- miR-1296 represents a potential therapeutic target for glioma treatment.
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