Proteomic analysis identifies argininosuccinate synthetase 1 and special AT-rich sequence binding protein 1 as reliable markers for the immunohistochemical distinction between WHO types A and B3 thymomas.

AIMS: The reliable classification of type A versus type B3 thymomas has prognostic and therapeutic relevance, but can be problematic due to considerably overlapping morphology. No immunohistochemical markers aiding in this distinction have been published so far. METHODS AND RESULTS: We identified and quantified numerous differentially expressed proteins using an unbiased proteomic screen by mass spectrometry in pooled protein lysates from three type A and three type B3 thymomas. From these, candidates were validated in a larger series of paraffin-embedded type A and B3 thymomas. We identified argininosuccinate synthetase 1 (ASS1) and special AT-rich sequence binding protein 1 (SATB1) as highly discriminatory between 34 type A and 20 type B3 thymomas (94% sensitivity, 98% specificity and 96% accuracy). Although not the focus of this study, the same markers also proved helpful in the diagnosis of type AB (n = 14), B1 (n = 4) and B2 thymomas (n = 10). CONCLUSIONS: Mutually exclusive epithelial expression of ASS1 in 100% of type B3 thymomas and ectopic nuclear expression of SATB1 in 92% of type A thymomas support the distinction between type A and type B3 thymomas with 94% sensitivity, 98% specificity and 96% accuracy.

SATB1 establishes ameloblast cell polarity and regulates directional amelogenin secretion for enamel formation.

BACKGROUND: Polarity is necessary for epithelial cells to perform distinct functions at their apical and basal surfaces. Oral epithelial cell-derived ameloblasts at secretory stage (SABs) synthesize large amounts of enamel matrix proteins (EMPs), largely amelogenins. EMPs are unidirectionally secreted into the enamel space through their apical cytoplasmic protrusions, or Tomes' processes (TPs), to guide the enamel formation. Little is known about the transcriptional regulation underlying the establishment of cell polarity and unidirectional secretion of SABs. RESULTS: The higher-order chromatin architecture of eukaryotic genome plays important roles in cell- and stage-specific transcriptional programming. A genome organizer, special AT-rich sequence-binding protein 1 (SATB1), was discovered to be significantly upregulated in ameloblasts compared to oral epithelial cells using a whole-transcript microarray analysis. The Satb1-/- mice possessed deformed ameloblasts and a thin layer of hypomineralized and non-prismatic enamel. Remarkably, Satb1-/- ameloblasts at the secretory stage lost many morphological characteristics found at the apical surface of wild-type (wt) SABs, including the loss of Tomes' processes, defective inter-ameloblastic adhesion, and filamentous actin architecture. As expected, the secretory function of Satb1-/- SABs was compromised as amelogenins were largely retained in cells. We found the expression of epidermal growth factor receptor pathway substrate 8 (Eps8), a known regulator for actin filament assembly and small intestinal epithelial cytoplasmic protrusion formation, to be SATB1 dependent. In contrast to wt SABs, EPS8 could not be detected at the apical surface of Satb1-/- SABs. Eps8 expression was greatly reduced in small intestinal epithelial cells in Satb1-/- mice as well, displaying defective intestinal microvilli. CONCLUSIONS: Our data show that SATB1 is essential for establishing secretory ameloblast cell polarity and for EMP secretion. In line with the deformed apical architecture, amelogenin transport to the apical secretory front and secretion into enamel space were impeded in Satb1-/- SABs resulting in a massive cytoplasmic accumulation of amelogenins and a thin layer of hypomineralized enamel. Our studies strongly suggest that SATB1-dependent Eps8 expression plays a critical role in cytoplasmic protrusion formation in both SABs and in small intestines. This study demonstrates the role of SATB1 in the regulation of amelogenesis and the potential application of SATB1 in ameloblast/enamel regeneration.

Special AT-rich sequence binding protein 1 is required for maintenance of T cell receptor responsiveness and development of experimental autoimmune encephalomyelitis.

The genome organizer special AT-rich sequence binding protein 1 (SATB1) regulates specific functions through chromatin remodeling in T helper cells. It was recently reported by our team that T cells from SATB1 conditional knockout (SATB1cKO) mice, in which the Satb1 gene is deleted from hematopoietic cells, impair phosphorylation of signaling molecules in response to T cell receptor (TCR) crosslinking. However, in vivo T cell responses upon antigen presentation in the absence of SATB1 remain unclear. In the current study, it was shown that SATB1 modulates T cell antigen responses during the induction and effector phases. Expression of SATB1 was upregulated in response to TCR stimulation, suggesting that SATB1 is important for this antigen response. The role of SATB1 in TCR responses and induced experimental autoimmune encephalomyelitis (EAE) was therefore examined using the myelin oligodendrocyte glycoprotein peptide 35-55 (MOG35-55) and pertussis toxin. SATB1cKO mice were found to be resistant to EAE and had defects in IL-17- and IFN-γ-producing pathogenic T cells. Thus, SATB1 expression appears necessary for T cell function in the induction phase. To examine SATB1 function during the effector phase, a tamoxifen-inducible SATB1 deletion system, SATB1cKO-ER-Cre mice, was used. Encephalitogenic T cells from MOG35-55-immunized SATB1cKO-ER-Cre mice were transferred into healthy mice. Mice that received tamoxifen before the onset of paralysis were resistant to EAE. Furthermore, no disease progression occurred in recipient mice treated with tamoxifen after the onset of EAE. Thus, SATB1 is essential for maintaining TCR responsiveness during the induction and effector phases and may provide a novel therapeutic target for T cell-mediated autoimmune diseases.

Special AT-rich sequence binding protein 1 promotes tumor growth and metastasis of esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma is one of the most aggressive malignancies worldwide. Special AT-rich sequence binding protein 1 is a nuclear matrix attachment region binding protein which participates in higher order chromatin organization and tissue-specific gene expression. However, the role of special AT-rich sequence binding protein 1 in esophageal squamous cell carcinoma remains unknown. In this study, western blot and quantitative real-time polymerase chain reaction analysis were performed to identify differentially expressed special AT-rich sequence binding protein 1 in a series of esophageal squamous cell carcinoma tissue samples. The effects of special AT-rich sequence binding protein 1 silencing by two short-hairpin RNAs on cell proliferation, migration, and invasion were assessed by the CCK-8 assay and transwell assays in esophageal squamous cell carcinoma in vitro. Special AT-rich sequence binding protein 1 was significantly upregulated in esophageal squamous cell carcinoma tissue samples and cell lines. Silencing of special AT-rich sequence binding protein 1 inhibited the proliferation of KYSE450 and EC9706 cells which have a relatively high level of special AT-rich sequence binding protein 1, and the ability of migration and invasion of KYSE450 and EC9706 cells was distinctly suppressed. Special AT-rich sequence binding protein 1 could be a potential target for the treatment of esophageal squamous cell carcinoma and inhibition of special AT-rich sequence binding protein 1 may provide a new strategy for the prevention of esophageal squamous cell carcinoma invasion and metastasis.

Special AT-rich sequence-binding protein 1: a novel biomarker predicting cervical squamous cell carcinoma prognosis and lymph node metastasis.

OBJECTIVE: Special AT-rich sequence-binding protein 1 is aberrantly expressed in various malignant tumors. However, the expression and function of special AT-rich sequence-binding protein 1 in cervical squamous cell carcinoma have not been reported. The objective of this study was to investigate the clinical significance of special AT-rich sequence-binding protein 1 in cervical squamous cell carcinoma. METHODS: In this study, we investigated the expression of special AT-rich sequence-binding protein 1 through immunohistochemistry in 25 normal cervix specimens and 167 cervical squamous cell carcinomas and analyzed its association with various clinicopathologic parameters, including patient outcome. RESULTS: Special AT-rich sequence-binding protein 1 protein was detected in 58 (34.7%) out of 167 patients and was highly related to International Federation of Gynecology and Obstetrics stage, histologic grade, lymph node metastasis, vascular-lymphatic invasion and recurrence of cervical squamous cell carcinoma. Patients with positive special AT-rich sequence-binding protein 1 expression had significantly lower overall survival and disease-free survival compared with patients with negative expression of special AT-rich sequence-binding protein 1 (P = 0.001 and P < 0.001, respectively). A multivariate Cox regression analysis revealed that special AT-rich sequence-binding protein 1 was an independent prognostic marker for both disease-free survival and overall survival of cervical squamous cell carcinoma patients (P = 0.038 and P = 0.010, respectively). A multivariate logistic regression analysis showed that special AT-rich sequence-binding protein 1 expression was strongly associated with lymph node metastasis (odds ratio = 2.497; P = 0.032). Sensitivity and specificity of special AT-rich sequence-binding protein 1 for lymph node metastasis were 61.0 and 73.8%, respectively. CONCLUSIONS: These results showed that special AT-rich sequence-binding protein 1 expression was associated with tumor progression, metastasis and poor prognosis in cervical squamous cell carcinoma. It may serve as a new prognostic biomarker or a target for improving the treatment efficiency of patients with cervical squamous cell carcinoma.

Downregulation of Ezh2 methyltransferase by FOXP3: new insight of FOXP3 into chromatin remodeling?

Transcription factor FOXP3 (forkhead box P3) is found initially as a key regulator in regulatory T cells. Recently its expression has been demonstrated in some non-lymphoid normal and cancerous cells. Now FOXP3 has been proven to regulate cancer-related genes, especially suppressor genes in breast cancer. But the mechanisms by which FOXP3 regulates suppressor genes are not fully determined. In this study, we found the inverse correlation between FOXP3 and Ezh2, an enzyme for histone H3K27 trimethylation (H3K27me3) and a central epigenetic regulator in cancer. The overexpression of FOXP3 weakened Ezh2's enhancement on the mammosphere formation, cell proliferation, directional migration, and colony forming ability of T47D cells. We demonstrated that FOXP3 could downregulate Ezh2 protein level and this depended on not only the FOXP3 expression amount, but also the nuclear localization of FOXP3. More importantly, we demonstrated FOXP3 accelerated Ezh2 protein degradation through the polyubiquitination-proteasome pathway by enhancing the transcription of E3 ligase Praja1 directly. These results provided a new mechanism for FOXP3 in histone modifications as an Ezh2 suppressor and supported new evidence for FOXP3 as a tumor suppressor in breast cancer.

Upregulation of ubiquitin carboxy­terminal hydrolase 47 (USP47) in papillary thyroid carcinoma ex vivo and reduction of tumor cell malignant behaviors after USP47 knockdown by stabilizing SATB1 expression in vitro.

Aberrant ubiquitination contributes to cancer development, including thyroid carcinoma. The present study assessed the expression of ubiquitin carboxy-terminal hydrolase 47 (USP47) and underlying molecular events in the development of papillary thyroid carcinoma (PTC). The effects of USP47 on PTC cell invasion and migration were analyzed by Transwell assays, while. the effects of USP47 and SATB1on PTC cell gene expression and changes in tumor cell metabolism were assayed by reverse transcription-quantitative PCR, western bolt, or ELISA, respectively. The expression of USP47 mRNA and protein was upregulated in PTC tissue and associated with the PTC tumor size. Knockdown of USP47 expression in PTC cell lines (TPC-1 and K1), decreased the cell proliferation mobility and invasion capacities, whereas USP47 overexpression in these cell lines showed an inverse effect and promoted cell glycolysis and glutamine metabolism. Moreover, expression of special AT-rich sequence-binding protein-1 (SATB1) was high in PTC tissue and was associated with USP47 expression. SATB1 expression promoted tumor cell glycolysis and glutamine metabolism, while USP47 protein bound to and deubiquitinated SATB1 to increase its intracellular levels, thus promoting glycolysis and glutamine metabolism. USP47 promotion of PTC development may be due to its stabilization of SATB1 protein, suggesting that targeting the USP47/SATB1 signaling axis may serve as a therapeutic intervention for PTC.

Long Non-Coding RNA ELFN1-AS1 Promoted Colon Cancer Cell Growth and Migration via the miR-191-5p/Special AT-Rich Sequence-Binding Protein 1 Axis.

Long non-coding RNAs (lncRNAs) are reported to participate in tumor development. It has been manifested in previous researches that lncRNA ELFN1-AS1 is involved in early-stage colon adenocarcinoma with potential diagnostic value. However, no studies have revealed the specific mechanism of ELFN1-AS1 in colon cancer, and there are no other studies on whether ELFN1-AS1 is associated with tumorigenesis. In our study, ELFN1-AS1 with high expression in colon cancer was selected by TCGA analysis, and the survival analysis was carried out to verify it. Subsequently, qRT-PCR was adopted for validating the results in tissues and cell lines. Cell counting kit-8 (CCK8), 5-ethynyl-2'-deoxyuridine (EdU), cell colon, cell apoptosis, cell cycle, cell migration, and invasion assays were utilized to assess the role of ELFN1-AS1 in colon cancer. Results uncovered that ELFN1-AS1 expression was prominently raised in colon cancer cells and tissues. ELFN1-AS1 decrement restrained cells to grow through interfering with distribution of cell cycle and promoting apoptosis. Meanwhile, ELFN1-AS1 decrement weakened the capacity of cells to migrate and invade. What's more, ELFN1-AS1 was uncovered to act as a competing endogenous RNA (ceRNA) to decrease miR-191-5p expression, thus raising special AT-rich sequence-binding protein 1 (SATB1), a downstream target of ceRNA. To sum up, ELFN1-AS1 drives colon cancer cells to proliferate and invade through adjusting the miR-191-5p/SATB1 axis. The above results disclose that lncRNA ELFN1-AS1 is possibly a novel treatment target for colon cancer cases.

The expression of special AT-rich binding protein 1 in cervical cancer and its clinical significance.

BACKGROUND: The oncogenic potential of special AT-rich binding protein 1 (SATB1) has been reported in various types of cancer, but its function in cervical cancer remains not fully investigated. This study aimed to investigate the effect of SATB1 mRNA expression on tumor progression and outcomes in the cervical cancer patients. METHODS: A total of 33 cervical cancer patients treated in our hospital from September 2012 to December 2015 were included. The mRNA expression level of STAB1 in cervical cancer tissue was determined by real-time PCR, and the patients were divided into dichotomous groups based on their SATB1 expression level. Clinical characteristics, recurrence, and survival outcomes were compared between groups. RESULTS: Compared with the SATB1-low group, the SATB1-high group had significantly advanced International Federation of Gynecology and Obstetrics (FIGO) stages (P=0.037) and histologic grade (P=0.036). Kaplan-Meier analysis showed that SATB1-high group had a worse overall survival (P=0.078, marginal significant). In the subgroup analysis of pathological types, adenocarcinomas group (n=8) had a significantly higher SATB1 expression level as compared with the squamous cell carcinomas (n=18) and adenosquamous carcinomas (n=7) groups (both P<0.05). Cervical squamous cell carcinomas patients with a high-expression SATB1 (n=8) had more advanced FIGO stages (P=0.015) and histologic grades (P=0.060, marginal significant) as well as a higher (P=0.069, marginal significant) incidence of lymphatic metastasis than those with a low expression of SATB1 (n=10). CONCLUSION: These results showed that expression of SATB1 may have an effect on the disease progression and survival outcome of cervical cancer.

miR-7-5p inhibits cell migration and invasion in glioblastoma through targeting SATB1.

MicroRNAs (miRNAs/miRs) have been revealed to influence the development and progression of glioblastoma. Although a number of miRNAs are abnormally expressed in glioblastoma it is not clear whether they are a factor associated with glioblastoma pathogenesis. In the present study, miR-7-5p was identified as being aberrantly downregulated in glioblastoma tissues and cell lines. miR-7-5p overexpression significantly decreased the migratory and invasive capacity of the cells, while miR-7-5p silencing had the opposite effect. In addition, a luciferase assay confirmed that special AT rich sequence binding protein 1 (SATB1) was a direct target gene of miR-7-5p in glioblastoma. The overexpression of SATB1 in glioblastoma was revealed to promote cell migration and invasion. In addition, SATB1 overexpression may weaken the inhibitory effect of miR-7-5p on cell migration and invasion. miR-7-5p overexpression reversed the effects of SATB1 on cell migration and invasion in glioblastoma cells. In conclusion, miR-7-5p may be a useful therapeutic target for the diagnosis and treatment of patients with glioblastoma.

Expression of SATB1 and E-cad in tissues of patients with endometrial carcinoma and the relationship with clinicopathological features.

The expression of special AT-rich sequence binding protein 1 (SATB1) and E-cadherin (E-cad) in tissues of patients with endometrial carcinoma and the relationships with clinicopathological features were investigated. One hundred and four cases of carcinoma tissues and 104 cases of para-carcinoma tissues of patients pathologically diagnosed as endometrial carcinoma in Affiliated Hospital of Jining Medical University (Jining, China) from August 2015 to August 2016 were selected. The expressions of SATB1 and E-cad in tissues was detected via streptavidin peroxidase biotin (SP) immunohistochemical method, and the relationship with clinicopathological features of patients was analyzed. SATB1 was positively expressed in 71 out of 104 cases of endometrial carcinoma tissues (the expression rate was 68.27%) and in 25 out of 104 cases of para-carcinoma tissues (the expression rate was 24.03%). The expression of SATB1 in endometrial carcinoma tissues was significantly higher than that in para-carcinoma tissues (P<0.05). E-cad was positively expressed in 60 out of 104 cases of carcinoma tissues (the expression rate was 57.6%) and 95 out of 104 cases of para-carcinoma tissues (the positive expression rate was 91.3%) (P<0.05). The expression of SATB1 and E-cad in endometrial carcinoma tissues was not associated with the menopausal status or age of patients (P>0.05), but correlated with the histological grade of endometrial carcinoma, depth of tumor invasion, lymph node metastasis and tumor lymph node metastasis (TNM) staging (P<0.05). In conclusion, SATB1 and E-cad play important roles in the occurrence and development of endometrial carcinoma, which are of great significance to the potential therapeutic target and prognosis estimation of endometrial carcinoma.

Ganodermanontriol inhibits expression of special AT rich sequence binding protein 1 gene in human hepatocellular carcinoma.

CONTEXT: The metastasis of liver cancer is a major cause of clinical treatment failure, restrain, and control the cancer metastasis is the major strategy of the treatment and prevention of the disease. Special AT-rich sequence-binding protein 1 (SATB1) gene was overexpressed in many malignant tumors and considered as a potential target of anticancer drug. This study investigated the mechanism how ganodermanontriol effect the expression of SATB1 and thus inhibits the growth and metastasis in hepatocellular carcinoma (HCC). AIMS: This study explored mainly on the mechanism how ganodermanontriol affects the expression of SATB1 and inhibits proliferation of tumor on human hepatoma cell line HepG2. SETTINGS AND DESIGN: The cancer cells were treated with ganodermanontriol. The status of the cells was detected by different methods. The mechanism was checked by various methods. MATERIALS AND METHODS: In HepG2 cancer cells treated with various concentrations of ganodermanontriol, the cell proliferation of was detected by MTT assay, cell apoptosis was analyzed by flow cytometry; the mRNA of SATB1, Bcl-2, Bax were detected by reverse transcription-polymerase chain reaction (RT-PCR) and the protein level of SATB1, Bcl-2, Bax, and caspase 3 were analyzed by Western blot. STATISTICAL ANALYSIS USED: Data are presented as the mean ± standard deviation. The data were analyzed using SPSS 18.0 software (SPSS, Inc., Chicago, IL, USA) and GraphPad Prism software (GraphPad Software, Inc., La Jolla, CA, USA). A one-way analysis of variance test was used to compare the differences among groups. RESULTS: This study showed that ganodermanontriol could significantly reduce the expression level of SATB1. CONCLUSION: Therefore, downregulate the cascade effect caused by the expression level of Bcl-2 in HCC HepG2 cells.

Inhibition of prostate cancer DU145 cell growth with small interfering RNA targeting the SATB1 gene.

Prostate cancer is a common visceral cancer of men worldwide. It is important to develop a more effective treatment for prostate cancer to overcome the treatment resistance that occurs with recurrence. RNA interference has been demonstrated to be a powerful tool for gene knockdown and has potential as a cancer treatment. It has been previously demonstrated that staining of special AT-rich sequence-binding protein 1 (SATB1) was stronger in prostatic carcinoma with metastasis compared with prostatic carcinoma without metastasis. In the present study, SATB1 small interfering (si)RNA was transfected into prostate cancer DU145 cells and normal human lung fibroblast cells, and cell proliferation was investigated using a Cell Counting kit-8. Three siRNA were transfected into cells using siPORT Lipid Transfection agent, and blank control and negative control groups were established. The cells were harvested and SATB1 mRNA and protein expression was determined by reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. DU145 cell adhesion, migration and invasion capabilities were determined using cell adhesion, Transwell and Transwell with Matrigel assays, respectively. Silencing SATB1 significantly inhibited DU145 cell growth, adhesion, migration and invasive capability in vitro, indicating that a SATB1-targeting siRNA was successfully engineered. The results of the present study suggest that SATB1 siRNA may be a potential agent for treating human prostate cancer.

Effect of SATB1 silencing on the proliferation, invasion and apoptosis of TE-1 esophageal cancer cells.

The aim of the present study was to investigate the effect of special AT-rich sequence-binding protein-1 (SATB1)-targeted small interfering RNA (siRNA) on the proliferation, invasion and apoptosis of TE-1 human esophageal cancer cells. SATB1 has been correlated with the metastasis and poor prognosis of colon and breast cancer, but the role of SATB1 in esophageal cancer remains unknown. Therefore, the present study constructed and transfected SATB1-siRNA into TE-1 cells in order to knockdown the expression of the SATB1 gene. Western blot analysis, a cell counting kit, transwell chamber assays and flow cytometry were used to assess the effect of SATB1-siRNA on the proliferation, invasion and apoptosis of cells. The results demonstrated that the expression of the SATB1 gene was efficiently knocked down by SATB1-siRNA, and that SATB1-siRNA inhibited the proliferation, invasion and apoptosis of TE-1 cells. Therefore, it was concluded that the SATB1 gene is important in the pathogenesis of human esophageal cancer, and may present a novel therapeutic target for esophageal cancer.

Inhibition of prostate cancer cell growth in vivo with short hairpin RNA targeting SATB1.

Despite previous advances, the treatment options for prostate cancer remain limited. For the purposes of gene knockdown, the utility of RNA interference has been demonstrated and is considered to have therapeutic potential. In the present study, a short hairpin RNA (shRNA) was used to assess the effect of special AT-rich sequence binding protein (SATB1) downregulation on the growth and metastatic potential of prostate cancer in xenograft nude mice. A plasmid carrying shRNA targeting SATB1, pSilencer-SATB1-shRNA, was successfully engineered. Using this plasmid, significant downregulation of SATB1 mRNA and protein expression in the DU145 prostate cancer cells was observed. pSilencer-SATB1-shRNA was demonstrated to be markedly efficacious against prostate cancer xenografts in nude mice. These results may lead to a novel method of improving gene therapy efficacy against prostate cancer via regulating the function of SATB1.

Expression and clinical significance of SATB1 and TLR4 in breast cancer.

This study investigated the expression of special AT-rich sequence-binding protein 1 (SATB1) and toll-like receptor 4 (TLR4) protein in breast cancer and its clinical significance. We collected breast cancer tissues from 120 patients and adjacent non-cancerous tissue from 53 patients. SATB1 was expressed in 89 cases of breast cancer (74.17%) and in 7 cases of adjacent non-cancerous tissue (13.21%). TLR4 was expressed in 70 cases of breast cancer tissues (58.33%) and in 48 cases of adjacent non-cancerous tissue (90.57%). The differences of SATB and TLR4 in breast cancer and adjacent non-cancerous tissue were statistically significant. We found a negative correlation between the expression of SATB1 and TLR4 (r=-0.624, P<0.05). The expression of SATB1 and TLR4 were not significantly correlated with age, menopause, and PR and HER-2 protein expression, but were significantly correlated with tumor size, local lymphatic metastasis, histopathological grade, tumor stage, and ER protein expression (P<0.05). Overall, SATB1 and TLR4 proteins are involved in the development of breast cancer, a finding of great significance to identify therapeutic targets and prognosis markers for breast cancer.

High expression of special AT-rich sequence binding protein-1 predicts esophageal squamous cell carcinoma relapse and poor prognosis.

Previous studies of the roles of special AT-rich sequence binding protein-1 (SATB1) in the development and progression of cancer have suggested that SATB1 promotes cancer cell metastasis. The aim of the present study is to evaluate the role of SATB1 in the progression and prognosis of esophageal squamous cell carcinoma (ESCC). ESCC tissues were collected from 102 patients and SATB1 mRNA expression was measured by reverse transcription-quantitative polymerase chain reaction. The association between expression of SATB1 mRNA with clinicopathological features and prognosis was assessed, and the prognosis of ESCC was evaluated using Kaplan-Meier survival curves. In the 102 ESCC tissues, SATB1 mRNA expression correlated with the clinical tumor node metastasis stage (P<0.05), but not with any other clinicopathological features (including age, gender, tumor differentiation grade, adjuvant radio/chemotherapy, or the consumption of alcohol and use of cigarettes) (P>0.05). The disease-free survival (DFS) and overall survival (OS) of patients with high SATB1 expression was decreased compared with those with low SATB1 expression. The present study indicated that SATB1 mRNA expression was associated with the postoperative recurrent and poor prognosis in ESCC. SATB1 may be a novel marker for predicting the recurrent and worse prognosis of ESCC.

Identification of SATB1 as a Specific Biomarker for Lymph Node Metastasis in Colorectal Cancer.

BACKGROUND/AIM: The integration of gene expression analysis and genomic profiling represents an efficient approach to the discovery of cancer-related genes. Lymph node metastasis (LNM) is a significant prognostic factor in colorectal cancer (CRC). Detection and analysis of factors related to LNM will help develop new diagnostic methods or therapies. In this study, we aimed to identify genes that are significantly related to LNM in CRC through integrated copy number analysis (CNA) and gene expression analysis. MATERIALS AND METHODS: Genes showing both up-regulated expression and copy number gains in cases involving CRC with LNM were extracted as candidate biomarkers. Expression of the mRNA of the final candidate was validated in 124 patients using quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays. Expression of the protein encoded by this candidate gene was assessed using immunohistochemical (IHC) staining of tissueσ from 328 patients. The association between protein expression and clinicopathological features was also examined. RESULTS: Special AT-rich sequence-binding protein 1 (SATB1) was extracted from integrated microarray analysis. SATB1 mRNA expression in cancer tissue was significantly higher in patients with LNM than without LNM. SATB1 protein overexpression was significantly associated with LNM. Moreover, overexpression of SATB1 was an independent poor prognostic factor in stage I-III, especially in stage II CRC. CONCLUSION: SATB1 may play an important role in LNM of CRC. SATB1 may be a biomarker of LNM and of recurrence after surgery for CRC.

Role of SATB1 in invasion and metastasis of human laryngeal squamous cell carcinoma cell line Hep-2 and its mechanisms / 国际生物医学工程杂志

Objective@#To investigate the role of special AT-rich sequence-binding protein 1 (SATB1) in invasion and metastasis of human laryngeal squamous cell carcinoma cell line Hep-2 and its mechanism.@*Methods@#Hep-2 cells were cultured in vitro. The cell lines were divided into two groups. The cells in the experimental group was transfected with Lipofectamine 2000 liposome for SATB1 small interfering RNA (SATB1-siRNA), and the cells in the control group was transfected with Lipofectamine 2000 liposome for NC-siRNA. The before and after transfection SATB1, E-cadherin and Snail genes relative expression levels between the two groups were detected and compared using RT-PCR. Transwell cell invasion experiments were applied to evaluate the cells invasive ability of the two groups. The scratch experiments were applied to evaluate the 48 h cell migration ability of the two groups.@*Results@#The differences in the relative expression level of SATB1, E-cadherin and Snail genes in pre-transfected laryngeal squamous cell line Hep-2 between the two groups were not statistically significant (all P>0.05). Compared with the control group, the relative expression levels of the mRNA of SATB1 and Snail genes decreased in the experimental group after transfection, while the relative expression levels of the mRNA of E-cadherin gene increased, and the differences were statistically significant (all P<0.05). After the transfection, the number of transwell membrane cells and cell migration distances of the two groups of cells decreased. The values of cell number and migration distance in the experimental group were lower than those in the control group, and the differences were statistically significant (all P<0.05).@*Conclusions@#SATB1 can promote the invasion and metastasis of Hep-2 cells, and its mechanism may be related to the down-regulation of E-cadherin and the up-regulation of Snail gene expression to induce epithelial-mesenchymal transition.

Role of SATB1 in invasion and metastasis of human laryngeal squamous cell carcinoma cell line Hep-2 and its mechanisms / 国际生物医学工程杂志

Objective To investigate the role of special AT-rich sequence-binding protein 1 (SATB1) in invasion and metastasis of human laryngeal squamous cell carcinoma cell line Hep-2 and its mechanism. Methods Hep-2 cells were cultured in vitro. The cell lines were divided into two groups. The cells in the experimental group was transfected with Lipofectamine 2000 liposome for SATB1 small interfering RNA (SATB1-siRNA), and the cells in the control group was transfected with Lipofectamine 2000 liposome for NC-siRNA. The before and after transfection SATB1, E-cadherin and Snail genes relative expression levels between the two groups were detected and compared using RT-PCR. Transwell cell invasion experiments were applied to evaluate the cells invasive ability of the two groups. The scratch experiments were applied to evaluate the 48 h cell migration ability of the two groups. Results The differences in the relative expression level of SATB1, E-cadherin and Snail genes in pre-transfected laryngeal squamous cell line Hep-2 between the two groups were not statistically significant (all P>0.05). Compared with the control group, the relative expression levels of the mRNA of SATB1 and Snail genes decreased in the experimental group after transfection, while the relative expression levels of the mRNA of E-cadherin gene increased, and the differences were statistically significant (all P<0.05). After the transfection, the number of transwell membrane cells and cell migration distances of the two groups of cells decreased. The values of cell number and migration distance in the experimental group were lower than those in the control group, and the differences were statistically significant (all P<0.05). Conclusions SATB1 can promote the invasion and metastasis of Hep-2 cells, and its mechanism may be related to the down-regulation of E-cadherin and the up-regulation of Snail gene expression to induce epithelial-mesenchymal transition.