Abstract
Glioblastoma (GBM) is the most common and aggressive of all brain tumors, with a median survival of only 14 months after initial diagnosis. Novel therapeutic approaches are an unmet need for GBM treatment. MicroRNAs (miRNAs) are a class of small non-coding RNAs that regulate gene expression at the post-transcriptional level. Several dysregulated miRNAs have been identified in all cancer types including GBM. In this study, we aimed to uncover the role of miR-143 in GBM cell lines, patient samples, and mouse models. Quantitative real-time RT-PCR of RNA extracted from formalin-fixed paraffin-embedded (FFPE) samples showed that the relative expression of miR-143 was higher in GBM patients compared to control individuals. Transient transfection of GBM cells with a miR-143 oligonucleotide inhibitor (miR-143-inh) resulted in reduced cell proliferation, increased apoptosis, and cell cycle arrest. SLC30A8, a glucose metabolism-related protein, was identified as a direct target of miR-143 in GBM cells. Moreover, multiple injections of GBM tumor-bearing mice with a miR-143-inh-liposomal formulation significantly reduced tumor growth compared to control mice. The reduced in vitro cell growth and in vivo tumor growth following miRNA-143 inhibition suggests that miR-143 is a potential therapeutic target for GBM therapy.
Highlights
Glioblastoma (GBM), known as glioblastoma multiforme, is the most common and lethal form of brain tumor [1]
Since the biological role of miR-143 in GBM is not well understood, rigorously investigated the role of miR-143 in GBM cell lines, patient samples, and a subcutaneous in the present study we rigorously investigated the role of miR-143 in GBM cell lines, patient samples, GBM mouse model
1). found to be significantly increased in GBM patients compared to controls (* p = 0.0208) (Figure 1)
Summary
Glioblastoma (GBM), known as glioblastoma multiforme, is the most common and lethal form of brain tumor [1]. There are no optimal treatments for this disease, which accounts for about 14,000 annual deaths in the U.S, having an incidence ratio of 2 to 3 out of 100,000 adults per year [2]. GBM tumors are known to be fast growing in the cerebral white matter and patients typically remain asymptomatic until advanced stages of the disease [6]. The current therapeutic strategy for GBM involves tumor resection surgery followed by radiotherapy (XRT) and/or radiosurgery in combination with temozolomide (TMZ)-based. Most GBM patients become resistant to a second round of TMZ (TMZ)-based chemotherapy [1,7]
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