Abstract
The functional significance of upregulation miR-34a in combination with albumin-bound paclitaxel nanoparticles in U251 glioblastoma cell line has been evaluated. The MTT assay determined that miR-34a and albumin-bound paclitaxel nanoparticles can reduce cell viability, but the combination of both factors has a stronger effect on cell viability. The application of qRT-PCR has demonstrated that the transduction of miR-34a could lead to exogenous upregulation of miR-34a level and downregulation of SURVIVIN. Moreover, treatment of U251 cells with miR-34a and nanoparticles together considerably inhibit SURVIVIN expression compared to miR-34a and nanoparticles alone. Flow cytometry showed that upon miR-34a overexpression cell cycle arrested in G1 phase, while treatment with nanoparticles increased the cell population in G2 phase. Upregulation of miR-34a along with treatment with nanoparticles elevated the number of cells arrested in G1/ G2 phases of the cell cycle. Expression of miR-34a with albumin-bound paclitaxel nanoparticles reduced cell viability, downregulated SURVIVIN and enhanced cell cycle arrest in G1/G2 phases. Thus, the upregulation of miR-34a with these nanoparticles are potential candidates therapeutic for glioblastoma cancer.
Highlights
Glioblastoma (GBM) is the most prevalent form of brain tumor which accounted for 15.4% of all primary brain tumors and about 60-70% of all astrocytomas (Sordillo, Sordillo, Helson, 2015)
After 24h the cells were treated with Temozolomide, paclitaxel, albumin-bound Paclitaxel Nanoparticles and Plex mir-34a
These results strongly suggested that overexpression of miR-34a in combination with albumin-bound paclitaxel nanoparticles can reduce the cell viability of glioblastoma cells in vitro
Summary
Glioblastoma (GBM) is the most prevalent form of brain tumor which accounted for 15.4% of all primary brain tumors and about 60-70% of all astrocytomas (Sordillo, Sordillo, Helson, 2015). The treatment of GBM is difficult due to the fact that tumors composed of a mix of different kinds of cells. MiRNAs regulate more than 60% of all human protein-coding genes and constitute an important regulatory network in all cell types. The key signaling pathways such as RAS, tumor protein 53, phosphoinositide kinase 3 (PIK3) pathways and along with factors that control cell cycle, have been known to be MicroRNAs ( known as miRNAs or miRs) are small non-coding RNAs, which their mature forms have 20-25 nucleotides long. They have both inducing and inhibitory function by targeting promoters and mRNAs (Rad et al, 2015). Most of the known miRNAs are identified to have an inhibitory function by suppressing the gene expression at the posttranscriptional level
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