Spalt-Like Transcription Factor 1 (SALL1) Gene Expression Inhibits Cell Proliferation and Cell Migration of Human Glioma Cells Through the Wnt/β-Catenin Signaling Pathway

Abstract

Background The spalt-like transcription factor 1 (SALL1) gene is a member of the Krüppel-associated box-containing zinc finger proteins (KRAB-ZFPs) and has been shown to modulate the onset and progression of human tumors. This study aimed to investigate the regulatory effects and mechanisms of SALL1 gene expression in human glioblastoma and glioma cells and tissue samples from patients with cerebral glioma. Material/Methods The human glioblastoma cell lines, LN229, U87-MG, U-251, U343, and the Hs683 glioma cell line were studied. The cell counting kit-8 (CCK-8) assay, cell cycle assay, wound-healing assay, transwell assay, Western blot, and quantitative real-time polymerase chain reaction (qRT-PCR) were used to evaluate cell proliferation, cell migration, and the cell cycle and expression of SALL1. Expression of SALL1 mRNA in 120 samples of cerebral glioma and 20 samples of normal brain were studied. Overall survival data from patients with cerebral glioma were analyzed. Results SALL1 expression was down-regulated in human glioblastoma and glioma cells and in cerebral glioma tissues. Down-regulation of SALL1 expression was associated with reduced overall survival. Overexpression of SALL1 was associated with inhibition of cell proliferation associated with cell cycle arrest at the G0/G1 phase. SALL1 inhibited cell migration by preventing epithelial-mesenchymal transition (EMT) and down-regulating the expression of stem cell markers. Reduced levels of β-catenin and downregulation of c-Myc and cyclin D1 and upregulation of p21and p27 expression were associated with SALL1 expression. Conclusions In human glioblastoma cells and cerebral glioma tissues, SALL1 acted as a tumor suppressor gene by inhibiting Wnt/β-catenin signaling.

Hsa_circ_0043265 Restrains Cell Proliferation, Migration and Invasion of Tongue Squamous Cell Carcinoma via Targeting the miR-1243/SALL1 Axis

“…Since the function of miRNAs are realized via modulating their target genes’ mRNA expression [ 26 ], we here conducted the bioinformatics analysis and verification experiment, and revealed that spalt like transcription factor 1 (SALL1) was one of the potential downstream target genes of miR-1243. The SALL1 is a member of Krüppel-associated box-containing zinc finger proteins (KRAB-ZFPs), and has been revealed to modulate the initiation and progression of human tumors [ 27 , 28 ]. SALL1 acted as a tumor suppressor gene in human glioma [ 27 ] and breast cancer ( Ma et al, 2018 ).…”

“…The SALL1 is a member of Krüppel-associated box-containing zinc finger proteins (KRAB-ZFPs), and has been revealed to modulate the initiation and progression of human tumors [ 27 , 28 ]. SALL1 acted as a tumor suppressor gene in human glioma [ 27 ] and breast cancer ( Ma et al, 2018 ). Further, miR-4286 may exert its tumor-promoting actions, in part, by downmodulating SALL1 in prostate cancer (PCa) [ 28 ].…”

Pro-inflammatory cytokine polymorphisms and interactions with dietary alcohol and estrogen, risk factors for invasive breast cancer using a post genome-wide analysis for gene–gene and gene–lifestyle interaction

“…One SNP near SALL1 , in relation to CRP, both overall and in the obesity strata, is associated with breast cancer risk. SALL1 is a member of the SALL gene family, encoding a multiple zinc-finger transcription repressor that regulates organogenesis and development of embryonic stem cells 69 – 71 . The role of the SALL genes (particularly SALL2 and SALL4 ) in tumorigenesis has recently been investigated as a tumor suppressor for ovarian and Wilms’ tumors 72 , 73 , hepatoblastoma, and gastric carcinoma 74 , 75 .…”

Transcription Factors: The Fulcrum Between Cell Development and Carcinogenesis

“…In cancer, Sall1 has been found to be downregulated in breast cancer, glioblastoma ( 77 ), and myeloid leukemia, supporting its role as a tumor suppressor ( 76 ). In support of such a tumor suppressor role, Sall1 has been found to be a target of oncogenic miRNAs.…”

“…Furthermore, overexpression of Sall1 negatively impacts cell cycle progression and proliferation through the suppression of β -catenin, antagonizing the Wnt/ β -catenin signaling pathway accordingly by targeting Wnt downstream targets Cyclin D1 (Ccnd1) and c-Myc oncogene. In addition, Sall1 is affecting the progression of cancer through the upregulation of the epithelial marker E-cadherin and downregulation of the mesenchymal markers vimentin and N-cadherin, driving mesenchymal-to-epithelial transition ( 77 ).…”