SATB1 enhances gastric cancer progression and metastasis via upregulation of CLIP4/DZIP1/ PRICKLE2 axis in gastric cancer patients

SATB1 (Special AT-rich sequence binding protein 1) plays key role in chromatin remodeling and geneexpression. SATB1 has been shown to promote invasion, migration and metastasis. However, the underlying molecular mechanisms, function and clinicopathological features of SATB1 in gastric cancer (GC) remains poorly understood. Here, we show that SATB1 plays critical role in GC progression. SATB1 upregulates in GC patients’ samples and shows co-apmlification with a subset of oncogenic proteins (PRICKLE2, ZEB1, CBWX7, WWTR1, ENAH, DZIP1, IGSF11, ZSCAN18, GFRA2, GFRA1, FGFR1, HDAC4, GHR, TIMP3, CLIP4, TAGLN and ILK) in different subtypes of GC. SATB1 shows positive correlation with GC promoting oncogenes and enhances the expression of metastasis associated genes in GC samples to potentiate GC progression. SATB1 enhances WNT/NOTCH signaling axis in GC samples. In contrast, STAB1 suppresses a network of tumor suppressor genes in GC samples. Moreover, SATB1 expression negatively correlates with GC patient’s survival. Importantly, we found that SATB1 co-amplified genes CLIP4, DZIP1 and PRICKLE2 independently involve in GC progression. Overexpression of CLIP4, DZIP1 and PRICKLE2 show poor survival rates in GC patients. DZIP1 empowers AKT3/FGF2/FGFR1 and CXCR3/CXCR6 in GC patients. PRICKLE2 enhances GC progression by targeting FGFR1/NOTCH3/WNT4 signaling. Taken together, these results identified novel roles of SATB1, CLIP4, DZIP1 and PRICKLE2 in the GC invasion, migration and metastasis using cancer bioinformatics approach. These results highlights clinical significance of SATB1, CLIP4, DZIP1 and PRICKLE2 in GC patients and furthermore, these proteins may serve as prognostic markers in GC. These results also provide SATB1, CLIP4, DZIP1 and PRICKLE2 as potential chemotherapeutic targets in treatment of gastric cancer patients.

SATB1, genomic instability and Gleason grading constitute a novel risk score for prostate cancer

Current prostate cancer risk classifications rely on clinicopathological parameters resulting in uncertainties for prognostication. To improve individual risk stratification, we examined the predictive value of selected proteins with respect to tumor heterogeneity and genomic instability. We assessed the degree of genomic instability in 50 radical prostatectomy specimens by DNA-Image-Cytometry and evaluated protein expression in related 199 tissue-microarray (TMA) cores. Immunohistochemical data of SATB1, SPIN1, TPM4, VIME and TBB5 were correlated with the degree of genomic instability, established clinical risk factors and overall survival. Genomic instability was associated with a GS ≥ 7 (p = 0.001) and worse overall survival (p = 0.008). A positive SATB1 expression was associated with a GS ≤ 6 (p = 0.040), genomic stability (p = 0.027), and was a predictor for increased overall survival (p = 0.023). High expression of SPIN1 was also associated with longer overall survival (p = 0.048) and lower preoperative PSA-values (p = 0.047). The combination of SATB1 expression, genomic instability, and GS lead to a novel Prostate Cancer Prediction Score (PCP-Score) which outperforms the current D’Amico et al. stratification for predicting overall survival. Low SATB1 expression, genomic instability and GS ≥ 7 were identified as markers for poor prognosis. Their combination overcomes current clinical risk stratification regimes.

Study on the Mechanism of miR-34a Affecting the Proliferation, Migration, and Invasion of Human Keloid Fibroblasts by Regulating the Expression of SATB1

Objectives. To explore the effect and mechanism of miR-34a on the proliferation, migration, and invasion of keloid fibroblasts (KFB). Methods. Isolate and culture KFB and normal skin fibroblast (NFB), detect the mRNA expression levels of miR-34a and integrin β5 (SATB1) in KFB and NFB by RT-qPCR, and detect SATB1 by western blot. The level of protein expression, MTT method, Transwell method, RT-qPCR, and western blot were used to detect the effects of overexpression of miR-34a or inhibition of SATB1 expression on the proliferation, migration, and invasion of KFB cells and the expression of related proteins. The dual luciferase reporter gene test verifies the targeting relationship between miR-34a and SATB1. Results. Compared with NFB, the expression of miR-34a was downregulated in KFB and the mRNA and protein expression levels of SATB1 were upregulated. Overexpression of miR-34a or inhibition of SATB1 expression inhibited the proliferation, migration, and invasion of KFB. miR-34a can negatively regulate the expression of SATB1, and overexpression of SATB1 reverses the effects of overexpression of miR-34a on the proliferation, migration, and invasion of KFB. Conclusions. miR-34a inhibits the proliferation, migration, and invasion of keloid fibroblasts by downregulating the expression of SATB1.

SATB homeobox 1 regulated genes in the mouse ectoplacental cone are important for placental development

ABSTRACTSATB homeobox 1 (SATB1) is abundantly expressed in the stem-state of trophoblast cells but downregulated during trophoblast differentiation. It is also expressed in high levels in the mouse ectoplacental cones (EPCs). We detected that SATB1 is involved in maintaining the self-renewal of trophoblast stem cells and inhibiting trophoblast differentiation. In this study, we have identified SATB1-regulated genes in the mouse EPC and analyzed their potential functions. A total of 1618 differentially expressed genes were identified in Satb1null EPCs by mRNA sequencing. Remarkably 90% of the differentially expressed genes were found to be upregulated in Satb1null EPCs suggesting a transcriptional repressor role of SATB1 in mouse trophoblast cells. Ingenuity Pathway Analyses demonstrated that the differentially expressed genes in Satb1null EPCs are particularly linked to WNT and TGFβ signaling pathways, which regulate self-renewal of stem cells and cell differentiation. Moreover, twenty-six of the EPC genes that are known to be involved in placental development including Eomes, Epas1, Fgfr2, Cdkn1c, and Plac9 were found dysregulated in Satb1null EPCs due to the loss of SATB1 expression. These genes are particularly involved in the formation of labyrinthine zone. Our results emphasize that SATB1-regulated genes in the mouse EPC contribute to key roles in the regulation of trophoblast differentiation and placental development.