P68 RNA helicase promotes invasion of glioma cells through negatively regulating DUSP5

Abstract

Gliomas are the most common central nervous system tumors. They show malignant characteristics indicating rapid proliferation and a high invasive capacity and are associated with a poor prognosis. In our previous study, p68 was overexpressed in glioma cells and correlated with both the degree of glioma differentiation and poor overall survival. Downregulating p68 significantly suppressed proliferation in glioma cells. Moreover, we found that the p68 gene promoted glioma cell growth by activating the nuclear factor‐κB signaling pathway by a downstream molecular mechanism that remains incompletely understood. In this study, we found that dual specificity phosphatase 5 (DUSP5) is a downstream target of p68, using microarray analysis, and that p68 negatively regulates DUSP5. Upregulating DUSP5 in stably expressing cell lines (U87 and LN‐229) suppressed proliferation, invasion, and migration in glioma cells in vitro, consistent with the downregulation of p68. Furthermore, upregulating DUSP5 inhibited ERK phosphorylation, whereas downregulating DUSP5 rescued the level of ERK phosphorylation, indicating that DUSP5 might negatively regulate ERK signaling. Additionally, we show that DUSP5 levels were lower in high‐grade glioma than in low‐grade glioma. These results suggest that the p68‐induced negative regulation of DUSP5 promoted invasion by glioma cells and mediated the activation of the ERK signaling pathway.

The DEAD-box helicase DDX56 is a conserved stemness regulator in normal and cancer stem cells

“…Other compounds, such as hippuristanol, selectively bind to and abolish both the RNA binding and ATPase activity of DDX2 (eIF4A) but leave ATP binding functionality unaffected (Lindqvist et al, 2008). Because DDX proteins are often multifunctional (Phung et al, 2019;Samir et al, 2019;Wang et al, 2019), some neoplasms may be responsive while others are not, similar to what we observe in GSCs 523 versus 564. Furthermore, in some cellular contexts, compartments, or cancers, targeting different domains may result in different effects on cellular fitness.…”

“…For example, DDX6 is essential for p-body homeostasis and pluripotency exit in mouse and human embryonic stem cells by regulating the translation of transcription factor and chromatin modifiers (Di Stefano et al, 2019). Other recent studies highlighted that DDX family members can be multifunctional in (Phung et al, 2019) as well as acting as a live-or-die cell-fate switch that modulates inflammasome activation (Samir et al, 2019), while DDX5 regulates both proliferation and migration of GBM through distinct pathways (Wang et al, 2019).…”

Linc00473 potentiates cholangiocarcinoma progression by modulation of DDX5 expression via miR-506 regulation

“…DDX5 also played important roles in promoting cancer cell proliferation and metastasis [24]. Published studies have shown that DDX5 enhances glioma cells invasion by negatively regulating DUSP5 [25]. Xue et al also found that DDX5 increased hepatocellular carcinoma cells growth through activating Akt signaling pathway [26].…”

Linc00473 potentiates cholangiocarcinoma progression by modulation of DDX5 expression via miR-506 regulation

“…DDX5 also played important roles in promoting cancer cell proliferation and metastasis [24]. Published studies have shown that DDX5 enhances glioma cells invasion by negatively regulating DUSP5 [25]. Xue et al [26] also found that DDX5 increased hepatocellular carcinoma cells growth through activating Akt signaling pathway.…”