Abstract
The Ankyrin repeat domain 49 (ANKRD49) is an evolutionarily conserved protein, which is related to mediate protein–protein interaction. However, the function of ANKRD49 in human glioma remains elusive. Mining through The Cancer Genome Atlas (TCGA) database, we found that the expression of ANKRD49 was increased in glioma tissues and that high expression of ANKRD49 was strongly associated with high disease grade and poor overall survival. To investigate the role of ANKRD49 in malignant glioma, lentivirus expressing shRNA targetting ANKRD49 was constructed in U251 and U87 malignant glioma cells. We demonstrated that ANKRD49 knockdown reduced the proliferation rate of U251 and U87 cells. Further mechanism analysis indicated that depletion of ANKRD49 led to the cell-cycle arrest and induced apoptosis in U251 and U87 cells. ANKRD49 knockdown also changed the expression of key effectors that are involved in stress response, cell cycle, and apoptosis, including p-HSP27 (heat shock protein 27), p-Smad2 (SMAD family member 2), p-p53, p-p38, p-MAPK (mitogen-activated protein kinase), p-SAPK/JNK (stress-activated protein kinase/c-jun n-terminal kinase), cleveagated Caspase-7, p-Chk1 (checkpoint kinase 1), and p-eIF2a (eukaryotic translation initiation factor 2a). Taken together, our findings implicate that ANKRD49 promotes the proliferation of human malignant glioma cells. ANKRD49 maybe an attractive target for malignant glioma therapy.
Highlights
Glioma is one of the most common tumors in the brain or spine that arises from the glial cells [1]
Through reanalyzing RNA sequencing data of glioma-related datasets in The Cancer Genome Atlas (TCGA) database, we found that the expression of Ankyrin repeat domain 49 (ANKRD49) was predominantly higher in glioma samples compared with matched normal samples (Figure 1A)
As cell cycle arrest may reflect the alterations of apoptosis, we evaluated the effect of ANKRD49 knockdown on apoptosis of U251 and U87 cells by annexin V-APC assay plus flow cytometry
Summary
Glioma is one of the most common tumors in the brain or spine that arises from the glial cells [1]. Glioblastoma, known as glioblastoma multiforme (GBM), has been considered as the most aggressive tumor in the brain, since the cells reproduce quickly and they are supported by a large network of blood vessels [4]. Prognosis of high-grade gliomas is generally poor with an average survival less than 12 months after diagnosis [5]. It is urgent and necessary to find effective therapies for gliomas [6]. Further understanding of the genetic and molecular mechanisms of gliomas will provide promising strategies for treatment of the diseases
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