Abstract

Purpose: To investigate the role of miR-455-3p in gliomas.
 Method: Quantitative real-time polymerase chain reaction was used to measure miR-455-3p and paired box 6 (PAX6) levels in glioma cell lines. Western blot analysis was used to determine the expression of cell cycle regulators. In addition to over-expression, silencing of miR-455-3p or PAX6 was performed to study the functions of miR-455-3p in gliomas.
 Results: The levels of miR-455-3p were significantly up-regulated in glioma cell lines (p < 0.05), while miR-455-3p over-expression increased glioma cell proliferation and interfered with the progress of the cell cycle (p < 0.01). Furthermore, endogenous miR-455-3p silencing prevented glioma cell proliferation by regulating cell cycle progression (p < 0.05).The results also showed that PAX6 controlled the cell cycle while PAX6 silencing selectively regulated p21 expression (p < 0.01). Furthermore, miR-455-3p and PAX6 influenced p53 expression. Re-introduction of PAX6 expressing vector into glioma cells rescued the pro-tumoral effect of miR-455-3p overexpression.
 Conclusion: These findings demonstrate the role of miR-455-3p as a tumour oncogene in gliomas via regulation of the cell cycle, indicating that miR-455-3p might act as a new treatment strategy for glioma cell tumours and a predictor of survival in glioma patients.

Highlights

  • Glioma is a type of malignant tumour of the central nervous system (CNS) that includes four clinical grades that are based on histology and prognosis [1,2]

  • The miR-455-3p levels in glioma cell lines A172, SW1783, U87, U251, and H4 was increased compared to normal human astrocytes (NHAS) (Figure 1)

  • Western blot assay showed that paired box 6 (PAX6) in glioma cell lines was markedly lower than that in astrocyte cell line (Figure 3 B)

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Summary

Introduction

Glioma is a type of malignant tumour of the central nervous system (CNS) that includes four clinical grades that are based on histology and prognosis [1,2]. Recent efforts have focused on new therapy strategies to MicroRNAs (miRNAs) comprise a large family of endogenous noncoding RNA molecules with approximately 20 nucleotides [2] These molecules cause translation inhibition or mRNA degradation, which result in biological effects in the body at the transcriptional and posttranscriptional levels via binding to the 3’untranslated region (3’-UTR) of target mRNAs [7]. Owing to their ability to modulate different target genes, miRNAs have crucial roles in diverse cellular behaviours in tumours, including proliferation, apoptosis, invasion, migration, and even glucose uptake [7]. MiRNAs are a kind of diagnostic and prognostic index of disease progression [1]

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