Background
Glioblastoma is one of the most common malignant brain tumors. Conventional clinical treatment of glioblastoma is not sufficient, and the molecular mechanism underlying the initiation and development of this disease remains unclear. Our study aimed to explore the expression and function of miR-873a-5p in glioblastoma and related molecular mechanism.
Methods
We analyzed the most dysregulated microRNAs from the Gene Expression Omnibus (GEO) database and examined the expression of miR-873-5p in 20 glioblastoma tissues compared with ten normal brain tissues collected in the Zhejiang Tongde Hospital. We then overexpressed or inhibited miR-873-5p expression in U87 glioblastoma cell lines and analyzed the phenotype using the cell counting kit-8 assay, wound healing assay, and apoptosis. In addition, we predicted upstream and downstream genes of miR-873-5p in glioblastoma using bioinformatics analysis and tested our hypothesis in U87 cells using the luciferase reporter gene assay and Western blotting assay. The differences between two groups were analyzed by Student's t test. The Kruskal-Wallis test was used for the comparison of multiple groups. A P < 0.05 was considered to be significant.
Results
The miR-873-5p was downregulated in glioblastoma tissues compared with that in normal brain tissues (normal vs. tumor, 0.762 ± 0.231 vs. 0.378 ± 0.114, t = 4.540, P < 0.01). Overexpression of miR-873-5p inhibited cell growth (t = 6.095, P < 0.01) and migration (t = 3.142, P < 0.01) and promoted cell apoptosis (t = 4.861, P < 0.01), while inhibition of miR-873-5p had the opposite effect. Mechanistically, the long non-coding RNA HOTAIRM1 was found to act as a sponge of miR-873-5p to activate ZEB2 expression in U87 cells.
Conclusions
We uncovered a novel HOTAIRM1/miR-873-5p/ZEB2 axis in glioblastoma cells, providing new insight into glioblastoma progression and a theoretical basis for the treatment of glioblastoma.
This work aimed to investigate the inter-regulatory functions of hsa-mir-127 and replication initiator 1 (REPIN1) on the proliferation and metastasis of glioma cells. The in-silico data on the implication of hsa-mir-127 and REPIN1 in glioma were retrieved from The Cancer Genome Atlas (TCGA). The expression levels of hsa-mir-127 and REPIN1 mRNA were determined by qRT-PCR, whereas Western blot was used to detect REPIN1 protein expression in glioma cell lines. The proliferation of glioma cells was determined by means of the MTT assay, whereas the transwell assay was employed for assessing the extent of cell migration and invasion. The interaction among REPIN1 and hsa-mir-127 was checked using the luciferase reporter assay. The expression of hsa-mir-127 was markedly increased in clinical data obtained from TCGA and in glioma cells compared with normal tissues and control cells, respectively. Increased expression of hsa-mir-127 and decreased expression of REPIN1 were both associated with poor overall survival. Moreover, hsa-mir-127 overexpression noticeably promoted proliferation, inhibited apoptosis and increased the invasive and migratory capacities of glioma cells. Inverse effects were found with hsa-mir-127 antisense inhibitor. Interestingly, overexpression of hsa-mir-127 downregulated REPIN1 expression, and luciferase reporter assay showed that the tumorigenesis effect of hsa-mir-127 requires, in part, its direct targeting of REPIN1. In conclusion, the hsa-mir-127/REPIN1 pathway is involved in gliomas and could be a potential therapeutic target.
Introduction:
In recent years, an increasing amount of literature has demonstrated the functional role of long non-coding RNA (lncRNA) in human diseases. LINC00515 is a newly defined lncRNA and is reported to act as an oncogene in multiple myeloma. However, the function of LINC00515 in glioma is still uncertain.
Materials and methods:
We examined the expression levels of LINC00515 in human glioma tissues and cell lines using real-time PCR analysis. In addition, we confirmed the distribution of LINC00515 in glioma cells and suppressed LINC00515 expression with siRNAs. CCK-8, colony formation assay and apoptosis analysis were used to study the function of LINC00515 in glioma progression. Then, we used bioinformatics prediction and subsequent experiments to reveal the underlying molecular mechanism.
Results:
We found that LINC00515 was up-regulated in glioma tissues and cell lines. LINC00515 was mainly located in the cytoplasm in glioma cells. Knockdown of LINC00515 led to decreased proliferation and increased apoptosis of glioma cells. Mechanistically, our data indicated that there was a LINC00515/miR-16/PRMT5 regulatory axis in glioma. LINC00515 could activate PRMT5 expression and promote glioma progression by acting as a sponge of miR-16.
Conclusion:
LINC00515 expression is elevated in human glioma and promotes growth and inhibits apoptosis of glioma cells. The regulatory cascade LINC00515/miR-16/PRMT5 plays a critical role in glioma progression.
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