OBJECTIVE: To investigate the role of MTBP in regulating the migration and invasion of human prostate cancer cells. METHODS: The baseline expressions of MTBP in 3 different human prostate cancer cells lines (22RV1, DU145 and Lncap) were detected using Western blotting. The cells were transfected with a small interfering RNA (siRNA) for MTBP knockdown or MTBP plasmid for MTBP overexpression, and 48 h later, the cells were examined for MTBP expression with Western blotting; the changes in the migration abilities of the cells were evaluated using wound healing assay and Transwell assay, and the cell invasiveness was assessed using Matrigel Transwell assay. The expression of E-cadherin protein, a marker of epithelial mesenchymal transition (EMT), was detected using Western blotting. RESULTS: MTBP expression was the highest in DU145 cells followed by Lncap cells, and was the lowest in 22RV1 cells, indicating a positive correlation of MTBP expression with the level of malignancy of human prostate cancer cells. Transfection of the cells with siRNA or MTBP plasmids efficiently lowered or enhanced the expressions of MTBP in human prostate cancer cells. Wound healing assay showed that inhibition of MTBP expression decreased the migration ability of the prostate cancer cells, and MTBP overexpression significantly promoted the migration of the cells ( < 0.01). Transwell assay showed that MTBP knockdown significantly lowered the migration and invasion ability of the cells, while MTBP overexpression markedly increased the number of migrating and invading cells ( < 0.01); Western blotting results showed that MTBP knockdown increased the expression of E-cadherin protein, and MTBP overexpression decreased E-cadherin expression in the prostate cancer cells. CONCLUSIONS MTBP overexpression promotes the migration and invasion of human prostate cancer cells possibly relation to the induction of EMT.
Antigens, CD ; metabolism ; Cadherins ; metabolism ; Carrier Proteins ; genetics ; metabolism ; Cell Line, Tumor ; Cell Movement ; Epithelial-Mesenchymal Transition ; Gene Expression Regulation, Neoplastic ; Gene Knockdown Techniques ; Humans ; Male ; Neoplasm Invasiveness ; Prostatic Neoplasms ; metabolism ; pathology ; RNA, Small Interfering ; Transfection

Antigens, Neoplasm ; genetics ; Apoprotein(a) ; genetics ; Carrier Proteins ; genetics ; Endometriosis ; metabolism ; pathology ; Endometrium ; metabolism ; pathology ; Female ; Humans ; Intracellular Signaling Peptides and Proteins ; genetics ; Membrane Proteins ; genetics ; Mutation, Missense ; genetics ; Nuclear Proteins ; genetics ; Ovarian Neoplasms ; metabolism ; pathology ; Proprotein Convertase 5 ; genetics ; Salivary Cystatins ; genetics ; Ubiquitin-Protein Ligases ; genetics ; Whole Exome Sequencing

OBJECTIVE: To investigate the transcriptional regulation of transcription factor MZF-1 on acute monocytic leukemia-related gene MLAA-34. METHODS: The effect of MZF-1 on the transcriptional activity of MLAA-34 gene promoter was analyzed by luciferase reporter gene detection system and site-directed mutation technique. The EMSA and ChIP assay were used to verify whether MZF-1 directly and specifically binds to the core region of MLAA-34 promoter. The over-expression vector and interference vector of MZF-1 were constructed to transfect U937 cells, and RT-PCR and Western blot were used to detect the transcription and expression changes of MLAA-34 gene. RESULTS: The transcription factor MZF-1 had a regulatory effect on MLAA-34 gene expression, and the relative luciferase activity was decreased after MZF-1 binding point mutation (P<0.01). EMSA and ChIP experiments demonstrated that MZF-1 could directly bind to MLAA-34 promoter and play a regulatory role. In the over-expression test, the increase of MZF-1 could up-regulate the expression of MLAA-34 (P<0.05). In the interference test, the decrease of MZF-1 could down-regulate the expression of MLAA-34 (P<0.05). CONCLUSION Transcription factor MZF-1 can bind to the transcriptional regulatory region on the promoter of MLAA-34 gene and promote the transcription of MLAA-34 gene in acute monocytic leukemia.
Antigens, Neoplasm ; genetics ; Apoptosis Regulatory Proteins ; genetics ; Gene Expression Regulation, Neoplastic ; Genes, Reporter ; Hepatocyte Nuclear Factor 1-alpha ; Humans ; Kruppel-Like Transcription Factors ; metabolism ; Leukemia, Monocytic, Acute ; Promoter Regions, Genetic ; Transcription, Genetic

OBJECTIVE: To explore the role of SIRT1 in the occurrence of epithelial-mesenchymal transition (EMT) in EC-9706 and Eca-109 cells and the possible mechanism. METHODS: Three chemically synthesized siRNA targeting SIRT1 were transfected into EC-9706 and Eca-109 cells with the non-transfected cells and cells transfected with the negative siRNAs as controls. Real-time PCR and Western blotting were used to detect the expressions of SIRT1, E-cadherin, vimentin, Snail, Twist1 and ZEB in the cells. Transwell invasion assay and wounding healing assay were used to examine the changes in the invasion and metastasis abilities of the cells after transfection. RESULTS: EC-9706 and Eca-109 cells transfected with SIRT1 siRNA1 and SIRT1 siRNA3 showed significantly decreased mRNA and protein expressions of SIRT1 ( < 0.05). Transwell invasion assay and wounding healing assay showed that transfection with SIRT1 siRNA1 and SIRT1 siRNA3 caused significantly lowered invasion and metastasis abilities in EC-9706 and Eca-109 cells ( < 0.05). In EC-9706 and Eca-109 cells transfected with SIRT1 siRNA1 and SIRT1 siRNA3, the expression level of E-cadherin was significantly increased while the expressions of vimentin, Snail and Twist were significantly lowered ( < 0.05). CONCLUSIONS SIRT1 participates in the invasion and metastasis of EC-9706 and Eca- 109 cells probably by inducing EMT via regulating the expression of Snail.
Antigens, CD ; metabolism ; Cadherins ; metabolism ; Cell Line, Tumor ; Cell Movement ; Epithelial-Mesenchymal Transition ; physiology ; Humans ; Neoplasm Invasiveness ; Nuclear Proteins ; metabolism ; RNA, Messenger ; metabolism ; RNA, Small Interfering ; metabolism ; Sirtuin 1 ; genetics ; metabolism ; Snail Family Transcription Factors ; metabolism ; Transfection ; Twist-Related Protein 1 ; metabolism ; Vimentin ; metabolism ; Zinc Finger E-box-Binding Homeobox 1 ; metabolism

Tumor-specific neoantigens have attracted much attention since they can be used as biomarkers to predict therapeutic effects of immune checkpoint blockade therapy and as potential targets for cancer immunotherapy. In this study, we developed a comprehensive tumor-specific neoantigen database (TSNAdb v1.0), based on pan-cancer immunogenomic analyses of somatic mutation data and human leukocyte antigen (HLA) allele information for 16 tumor types with 7748 tumor samples from The Cancer Genome Atlas (TCGA) and The Cancer Immunome Atlas (TCIA). We predicted binding affinities between mutant/wild-type peptides and HLA class I molecules by NetMHCpan v2.8/v4.0, and presented detailed information of 3,707,562/1,146,961 potential neoantigens generated by somatic mutations of all tumor samples. Moreover, we employed recurrent mutations in combination with highly frequent HLA alleles to predict potential shared neoantigens across tumor patients, which would facilitate the discovery of putative targets for neoantigen-based cancer immunotherapy. TSNAdb is freely available at http://biopharm.zju.edu.cn/tsnadb.
Antigens, Neoplasm ; metabolism ; Data Analysis ; Databases, Genetic ; Humans ; Immunotherapy ; Mutation ; genetics ; Neoplasms ; genetics ; immunology ; Tumor Suppressor Protein p53 ; genetics ; Urinary Bladder Neoplasms ; genetics

T-cell receptor (TCR)-engineered T cells are a novel option for adoptive cell therapy used for the treatment of several advanced forms of cancer. Work using TCR-engineered T cells began more than two decades ago, with numerous preclinical studies showing that such cells could mediate tumor lysis and eradication. The success of these trials provided the foundation for clinical trials, including recent clinical successes using TCR-engineered T cells to target New York esophageal squamous cell carcinoma (NY-ESO-1). These successes demonstrate the potential of this approach to treat cancer. In this review, we provide a perspective on the current and future applications of TCR-engineered T cells for the treatment of cancer. Our summary focuses on TCR activation and both pre-clinical and clinical applications of TCR-engineered T cells. We also discuss how to enhance the function of TCR-engineered T cells and prolong their longevity in the tumor microenvironment.
Animals ; Antigens, Neoplasm ; immunology ; metabolism ; Humans ; Neoplasms ; immunology ; metabolism ; Receptors, Antigen, T-Cell ; genetics ; metabolism ; T-Lymphocytes ; immunology ; metabolism

OBJECTIVETo explore the role of endothelin-1 (ET-1) gene in regulating the proliferation, migration and invasion of nasopharyngeal carcinoma cells.

METHODSA lentivirus-mediated shRNA-ET-1 vector was infected into 5-8F cells, and the interference efficiency was examined with Western blotting. MTT assay, cell cycle analysis, plate colony formation assay, Transwell assay, Boyden chamber assay and tumor growth assay were carried out to analyze the changes in cell proliferation, migration and invasion. The expressions of genes related with epithelial-mesenchymal transition (EMT) were examined using Western blotting.

RESULTSshRNA-ET-1 transfection significantly inhibited the expression of ET-1, and suppressed the growth, migration and invasion of 5-8F cells. ET-1 knockdown enhanced the expression of E-cadherin and CK18 and inhibited the expression of N-cadherin and vimentin.

CONCLUSIONET-1 promotes cell growth, migration and invasion by modulating the genes associated with epithelial-mesenchymal transition in nasopharyngeal carcinoma cells.

Antigens, CD ; metabolism ; Cadherins ; metabolism ; Carcinoma ; genetics ; pathology ; Cell Cycle ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Endothelin-1 ; genetics ; Epithelial-Mesenchymal Transition ; Gene Silencing ; Humans ; Lentivirus ; Nasopharyngeal Neoplasms ; genetics ; pathology ; Neoplasm Invasiveness ; RNA, Small Interfering ; genetics ; Transfection ; Vimentin ; metabolism

OBJECTIVETo investigate the effect of small interfering RNA (siRNA)-mediated silencing of PC4 and SFRS1 interacting protein 1 (PSIP1) on invasion and migration of human glioma U87 cells.

METHODSChemically synthesized siRNA targeting PSIP1 gene was transfected into U87 cells via lipofectamine, and the gene silencing effect was determined using real-time PCR. The changes in the invasion and migration abilities of the transfected cells were assessed with Transwell assay and wound healing assay, respectively. Western blotting was used to analyze the expression of N-cadherin, β-catenin and the transcription factor Slug.

RESULTSThe mRNA and protein level of PSIP1 was significantly reduced in U87 cells after transfection with PSIP1 siRNA (P<0.0001). PSIP1 knockdown in U87 cells resulted in significant suppression of cell invasion and migration abilities (P<0.01) and also reduced N-cadherin, β-catenin and Slug expressions.

CONCLUSIONs Silencing of PSIP1 impairs the invasion and migration abilities of glioma cells and lowers the expressions of N-cadherin, β-catenin and Slug, suggesting that PSIP1 may regulate Slug by classical Wnt/β-catenin signaling pathway to modulate epithelial-mesenchymal transition and promote the invasion and migration of glioma cells.

Adaptor Proteins, Signal Transducing ; genetics ; metabolism ; Antigens, CD ; metabolism ; Cadherins ; metabolism ; Cell Line, Tumor ; Cell Movement ; Epithelial-Mesenchymal Transition ; Glioma ; pathology ; Humans ; Neoplasm Invasiveness ; RNA Interference ; RNA, Messenger ; genetics ; metabolism ; RNA, Small Interfering ; genetics ; Real-Time Polymerase Chain Reaction ; Snail Family Transcription Factors ; Transcription Factors ; genetics ; metabolism ; Transfection ; Wnt Signaling Pathway ; beta Catenin ; metabolism

Transforming growth factor (TGF)-β signaling plays an important role in the pathogenesis of psoriasis. CD109, a novel TGF-β co-receptor, which inhibits TGF-β signaling by enhancing Smad7-dependent degradation of TGF-β type I receptor (TGF-β RI), is abnormally expressed in psoriasis. To date, the expression of Smad7 and the correlation between CD109 and Smad7 expression in psoriasis have not been fully elucidated. This study was designed to investigate the expression and the correlation of CD109 and TGF-β signaling associated proteins in psoriasis and their roles in the pathogenesis of psoriasis. Thirty-two psoriasis specimens were subjected to immunohistochemical staining for CD109, Smad7, TGF-β RI and Ki67. Ten normal skin (NS) specimens served as controls. The positive expression rate (% positive cells) of Smad7 and Ki67 in psoriasis was significantly higher than in NS (62.6%±19.9% vs. 17.2%±4.4%, and 50.7%±14.3% vs. 19.5%±3.2%, respectively, P<0.001), and the expression levels of CD109 and TGF-β RI were reduced significantly in psoriasis as compared with NS (8.1%±6.7% vs. 35.8%±6.7% and 27.3%±3.4% vs. 3.0%±3.4%, respectively, P<0.001). There were significantly negative correlations between CD109 and Smad7 (r=-0.831, P<0.01). These findings indicated that CD109 might play a certain role in the pathogenesis of psoriasis. Lower expression of CD109 and TGF-β RI was highly correlated with higher expression of Smad7 and Ki67, suggesting that CD109 may induce the pathogenesis of psoriasis through Smad7-mediated degradation of TGF-β RI, and lead to the termination of TGF-β signaling.
Adolescent ; Adult ; Antigens, CD ; genetics ; metabolism ; Case-Control Studies ; Down-Regulation ; Female ; GPI-Linked Proteins ; genetics ; metabolism ; Humans ; Male ; Middle Aged ; Neoplasm Proteins ; genetics ; metabolism ; Psoriasis ; metabolism ; pathology ; Signal Transduction ; Smad7 Protein ; genetics ; metabolism ; Transforming Growth Factor beta ; metabolism ; Up-Regulation

OBJECTIVETo study the antiapoptotic effect of leukemia-associated gene MLAA-34 in HeLa cells.

METHODSThe MLAA-34 recombinant lentiviral expression vector was constructed, and the stably transfected HeLa cell line with high expression of MLAA-34 was set up; As(2)O(3) was used to induce apoptosis; the MTT assay, colony formation test and flow cytometry were used to detect the ability of cell proliferation, colong formation, apoptosis and cell cycle changes respectively.

RESULTSAfter treatment with As(2)O(3), the survival rate of HeLa cells with MLAA-34 overexpression was significantly higher than that of the control cells, and the colony formation ability of MLAA-34 significantly increased, and the high expression of MLAA-34 gene significantly decreased the apoptosis rate of HeLa cells, and decreased the proportion of G(2)/M phase cells.

CONCLUSIONThe leukemia-associated gene MLAA-34 has been comfirmed to show antiapoptotic effect in HeLa cells which are induced by As(2)O(3).

Antigens, Neoplasm ; genetics ; metabolism ; Apoptosis ; Apoptosis Regulatory Proteins ; genetics ; metabolism ; Arsenicals ; Cell Cycle ; Cell Proliferation ; HeLa Cells ; Humans ; Lentivirus ; Oxides ; Transfection