Abstract
BackgroundLATS1 is a tumor suppressor genes implicated in the pathogenesis of certain types of tumors, but its role is not known in human glioma.MethodsUsing real-time PCR and immunohistochemistry, we detected the mRNA and protein expression of LATS1 in glioma. The effect of LATS1 on cell growth and invasion were investigated.ResultsWe found that mRNA and protein of LATS1 expression is significantly downregulated in glioma compared with normal control brain tissues. Furthermore, reduced LATS1 expression was markedly negatively correlated with WHO grade and KPS (p<0.001 and p<0.001) in glioma patients. Patients with lower LATS1 expression had a significantly shorter overall survival time than did patients with higher LATS1 expression. Multivariate analysis suggested that the level of LATS1 expression was an independent prognostic indicator (p<0.001) for the survival of patients with glioma. Forced expression of LATS1 in glioma U251 cells not only significantly suppressed cell growth, migration and invasion, but retarded cell cycle progression from G2/M to G1 in vitro. Finally, we found that overexpressed LATS1 markedly inhibited the expression level of cell cycle factor CCNA1.ConclusionThese results indicate that LATS1 is an important candidate tumor suppressor and its downregulated expression may contribute to glioma progression.
Highlights
LATS1 is a tumor suppressor genes implicated in the pathogenesis of certain types of tumors, but its role is not known in human glioma
Downregulated mRNA expression of LATS1 in Glioma In order to assess the role of LATS1 in glioma, we performed real-time PCR to measure the expression of LATS1 mRNA transcripts in 17 paired gliomas and their adjacent brain tissues
LATS1 inhibits the expression of CCNA1 In exploring the molecular mechanism of LATS1 tumorsuppressing function in glioma, we found that restoration of LATS1 expression significantly inhibited expression of cell cycle factor CCNA1 in glioma U251 cells (Figure 4D)
Summary
LATS1 is a tumor suppressor genes implicated in the pathogenesis of certain types of tumors, but its role is not known in human glioma. The molecular pathogenesis of malignant gliomas is still unclear, a major research effort has been directed at identifying novel specific glioma-associated genes which might play significant roles in glioma carcinogenesis. The LATS1 gene, a mammalian homolog of fly LATS originally isolated in Drosophila as a cell proliferation inhibitor [4,5], is a speculative serine/threonine kinase that localizes to the mitotic apparatus. Based on Takahashi et al’s report that the LATS1 gene promoter is hypermethylated in the glioma U251 cell line [13], we hypothesized that expression of LATS1 gene is decreased in glioma pathogenesis. We examined the expression of LATS1 in gliomas and explored its role as a tumor-suppressor gene in glioma cells in vitro. We provided a preliminary molecular mechanism of LATS1-mediated cell growth suppression in glioma
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