ARPP-19 promotes proliferation and metastasis of human glioma

Abstract

Glioma is the most common and aggressive type of human primary brain tumor with a poor outcome. The molecular mechanisms underlying glioma development and progression are still poorly understood. Recent studies have reported a novel role of ARPP-19 in the regulation of cell mitosis and cancer progression. However, no study has been carried out to determine the role of ARPP-19 in human glioma cells and assess the expression and clinical significance of ARPP-19 in human glioma. In this study, we systematically examined the role of ARPP-19 in glioma A172 cells and examined the expression of ARPP-19 and CD147 in 81 cases of human glioma tissue specimens and correlated them to clinicopathological parameters and patient survival. We found that ARPP-19 promoted both proliferation and metastasis of human glioma cells and the expression of ARPP-19 and CD147 in high-grade glioma was significantly higher than that in the low-grade glioma. Patients whose tumors were positive for expression of ARPP-19 or CD147 showed lower relapse-free survival and overall survival than patients whose tumors were negative for ARPP-19 or CD147, respectively. Pearson correlation analysis indicated that there was a statistically significant correlation between ARPP-19 and CD147. Expressions of ARPP-19 and CD147 may serve as biomarkers for high-grade glioma and poor patient survival.

CMIP Promotes Proliferation and Metastasis in Human Glioma

“…RT-qPCR was used to determine the mRNA levels of CMIP in different human glioma cell lines, which was performed as described in previous studies using SYBR Premix Ex Taq Kit (Takara) [3]. GAPDH was used as a control.…”

“…Cell migration assay and invasion assay were performed to determine cell metastasis. They were all carried out as described previously [3, 19]. In MTT assay, cells were plated into 96-well plates with an original number of 2000 and tested using OD490 values after 1, 2, 3, and 4 days.…”

“…In this study, protein level of CMIP (Proteintech 12851-1-AP1:1000) and MDM2 (Santa Cruz sc-53041:1000) in A172 and U251 cells were determined by Western blot analysis, as described in previous studies [3]. α -Tubulin (Proteintech 66031-1-Ig 1:5000) was used as a control.…”

“…Conventional treatments for glioma including surgical resection, radiation, and chemotherapy have shown limited impact [3, 4]. Even with optimal treatment, the average survival of glioma patients is no more than 1.5 years and the 5-year survival rate no more than 5% [4–6].…”

ARPP19 Phosphorylations by PKA and Greatwall: The Yin and the Yang of the Cell Decision to Divide

“…Gwl then phosphorylates two proteins from the endosulfine (ENSA) family: α-endosulfine and its very close paralog ARPP19 at an S residue present in a highly conserved KYFDSGDY motif, corresponding to S67 in Xenopus ARPP19 [20,21,28]. These small proteins are expressed ubiquitously in neurons as well as in nonneuronal cells and regulate a plethora of biological processes including insulin secretion, quiescence upon nutrient deprivation in yeast and neurite outgrowth [28][29][30][31][32][33][34]. Interestingly, these proteins preset the biochemical characteristics of phosphatase inhibitors, being basic-, heat-and acid-stable.…”