Transcription factor SNAI2 exerts pro-tumorigenic effects on glioma stem cells via PHLPP2-mediated Akt pathway

Abstract

The current study aimed to investigate the effects associated with SNAI2 on the proliferation of glioma stem cells (GSCs) to elucidate its underlying molecular mechanism in the development of glioma. The expression of Snail family transcriptional repressor 2 (SNAI2) in glioma tissues was initially predicted via bioinformatics analysis and subsequently confirmed by reverse transcription quantitative polymerase chain reaction (RT-qPCR), which revealed that SNAI2 was highly expressed in glioma tissues as well as GSCs, with an inverse correlation with overall glioma patient survival detected. Loss- and gain- of-function assays were performed to determine the roles of SNAI2 and pleckstrin homology domain and leucine rich repeat protein phosphatase 2 (PHLPP2) on GSC viability, proliferation and apoptosis. Data were obtained indicating that SNAI2 promoted the proliferation of GSCs, while overexpressed PHLPP2 brought about a contrasting trend. As detected by chromatin immunoprecipitation, RT-qPCR and agarose gel electrophoresis, SNAI2 bound to the promoter region of PHLPP2 and repressed the transcription of PHLPP2 while SNAI2 was found to inhibit PHLPP2 resulting in activation of the Akt pathway. Finally, the roles of SNAI2 and PHLPP2 were verified in glioma growth in nude mice xenografted with tumor. Taken together, the key findings of the present study suggest that SNAI2 may promote the proliferation of GSCs through activation of the Akt pathway by downregulating PHLPP2.

A novel risk model based on anoikis: Predicting prognosis and immune infiltration in cutaneous melanoma

“…Here, the high expressions of SNAI2 and TFDP1 were observed in the high-risk score patients; however, the expression of IKBKG and MCL1 was lower. Snail family transcriptional repressor 2(SNAI2), a member of the Snail family, was regarded as an epithelial-to-mesenchymal transition-inducing transcription factor (Peng et al, 2022); (Jin et al, 2022). Extensive research has shown that SNAI2 Frontiers in Pharmacology frontiersin.org plays a critical role in melanocytes, adipocytes, and germ cells, contributing to cell differentiation and tumor initiation (Zhao et al, 2016).…”

The value of cuproptosis-related differential genes in guiding prognosis and immune status in patients with skin cutaneous melanoma

“…SNAI2 has been implicated in the diseases of melanocytes development and a variety of cancers ( Cobaleda et al, 2007 ). SNAI2 plays a crucial role in regulating T-cell lineages ( Pioli et al, 2016 ) and cancer cell stemness ( Chen et al, 2021 ; Peng et al, 2022 ), as well as modulating lapatinib resistance in HER2-positive breast cancer ( Hamalian et al, 2021 ) and enhancing 5-fluorouracil sensitivity in colorectal cancer ( Findlay et al, 2014 ). We developed a risk-scoring model for SKCM patients according to seven cuproptosis-related differential genes, using a training set to distinguish between low -risk and high -risk groups.…”

The promoting effect and mechanism of MAD2L2 on stemness maintenance and malignant progression in glioma

“…For sorting GCSs from U87 and LN229 cells by flow cytometry [ 29 ], after harvesting cells and resuspend with PBS, incubated the cells with anti-CD133 antibody (#60577S, Cell Signaling Technology) for 30 min at 4 ℃, protected from light. Following this, the cells were centrifuged at 1000 rpm for 5 min and subsequently resuspended in 100 μL of PBS.…”