Abstract
BackgroundTransgelin-2 (TAGLN2) is a member of the calponin family of actin-bundling proteins that is involved in the regulation of cell morphology, motility, and cell transformation. Here, the clinical significance and potential function of TAGLN2 in malignant gliomas were investigated.MethodsMolecular and clinical data was obtained from The Cancer Genome Atlas (TCGA) database. Gene ontology and pathway analysis was used to predict potential functions of TAGLN2. RNA knockdown was performed using siRNA or lentiviral contructs in U87MG and U251 glioma cell lines. Cells were characterized in vitro or implanted in vivo to generate orthotopic xenografts in order to assess molecular status, cell proliferation/survival, and invasion by Western blotting, flow cytometry, and 3D tumor spheroid invasion assay, respectively.ResultsIncreased TAGLN2 expression was associated with increasing tumor grade (P < 0.001), the mesenchymal molecular glioma subtype and worse prognosis in patients (P < 0.001). Immunohistochemistry performed with anti-TAGLN2 on an independent cohort of patients (n = 46) confirmed these results. Gene silencing of TAGLN2 in U87MG and U251 significantly inhibited invasion and tumor growth in vitro and in vivo. Western blot analysis revealed that epithelial-mesenchymal transition (EMT) molecular markers, such as N-cadherin, E-cadherin, and Snail, were regulated in a manner corresponding to suppression of the EMT phenotype in knockdown experiments. Finally, TAGLN2 was induced ~ 2 to 3-fold in U87MG and U251 cells by TGFβ2, which was also elevated in GBM and highly correlated with TAGLN2 mRNA levels (P < 0.001).ConclusionsOur findings indicate that TAGLN2 exerts a role in promoting the development of human glioma. The regulation and function of TAGLN2 therefore renders it as a candidate molecular target for the treatment of GBM.
Highlights
Transgelin-2 (TAGLN2) is a member of the calponin family of actin-bundling proteins that is involved in the regulation of cell morphology, motility, and cell transformation
Increased expression of TAGLN2 is associated with increasing tumor grade in glioma To begin to define the function of TAGLN2 in glioma development, gene expression levels of TAGLN2 were analyzed in glioblastoma multiforme (GBM) and low grade gliomas (LGGs) as well as normal brain tissues from the The Cancer Genome Atlas (TCGA) dataset
TAGLN2 mRNA levels were significantly increased in GBMs compared to LGGs and normal brain tissues in TCGA (P < 0.001; Fig. 1a)
Summary
Transgelin-2 (TAGLN2) is a member of the calponin family of actin-bundling proteins that is involved in the regulation of cell morphology, motility, and cell transformation. The clinical significance and potential function of TAGLN2 in malignant gliomas were investigated. Human gliomas are the most common and deadly type of primary intracranial tumors and account for approximately 80% of all primary brain malignancies. Gliomas are histopathologically classified into four tumor grades (I–IV) according to the World Health Organization (WHO). Whole-genome analysis of patient cases through The Cancer Genome Atlas (TCGA), revealed a molecular classification scheme for GBM which includes four molecular subtypes: proneural, neural, classical, and mesenchymal. Among these four subtypes, the mesenchymal subtype was distinguished from the others as being aggressive [3,4,5]. There is an urgent need for the exploration of novel biomarkers and
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