miR-362-3p inhibited the invasion and metastasis of oral squamous cell carcinoma cells by targeting the regulation of pituitary tumor-transforming gene 1.

OBJECTIVES: This study aimed to explore the effect of pituitary tumor-transforming gene 1 (PTT-G1) on the invasion and proliferation of oral squamous cell carcinoma (OSCC) cell lines under the action of miR-362-3p. METHODS: The bioinformatics online database was used to query the expression of PTTG1 in head and neck squamous cell carcinoma (HNSCC). The expression of PTTG1 in the Cal-27, HN-30, and HOK cell lines was detected by Western blot. A wound-healing assay was used to determine the effect of PTTG1 on the migration ability of the OSCC cells. The Transwell assay was used to examine the changes in cell-invasion ability. 5-ethynyl-2'-deoxyuridine (EdU) cell-proliferation assay was used to detect changes in cell-proliferation ability. Bioinformatics approach predicted the upstream miRNA of PTTG1. The targeting relationship between miR-362-3p and PTTG1 was examined by the dual luciferase assay, and quantitative real-time polymerase chain reaction (qRT-PCR) was used to determine the expression of miRNA in OSCC tissues. RESULTS: The ENCORI database showed that PTTG1 expression was up-regulated in OSCC tissues. Western blot confirmed that PTTG1 expression was up-regulated in Cal-27 and HN-30 cells than HOK cells. PTTG1 knockout can inhibit the migration, invasion, and proliferation of Cal-27 and HN-30 cells (P<0.05). Bioinformatics prediction websites predicted that the upstream miRNA of PTTG1 was miR-362-3p, and PTTG1 can bind to miR-362-3p. Results of qRT-PCR showed that miR-362-3p expression was downregulated in OSCC tissues compared with normal tissue (P<0.05). Transwell and EdU experiments confirmed that miR-362-3p knockdown can promote the invasion and proliferation of Cal-27 and HN-30 after PTTG1 knockdown. CONCLUSIONS: miR-362-3p can inhibit the invasion and proliferation of Cal-27 and HN-30 cells by targeting PTTG1.

Upregulated expression of PTTG1 is associated with progression of pancreatic cancer.

Background: Pancreatic cancer (PC) is an aggressive disease with a very poor prognosis. The insidious onset, rapid progression, and resistance to conventional therapies mark the imperious need for novel biomarkers and therapeutic targets. The pituitary tumor transforming gene 1 (PTTG1), implicated in tumorigenesis and cellular transformation, has been studied in various cancers, however, its role and mechanisms in PC remain to be elucidated for better understanding the disease pathology and in enhancing patient management strategies. Methods: The present study examined the PTTG1 messenger RNA (mRNA) expression levels and clinical significance through meta-analysis based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Immunohistochemistry (IHC) was used to measure PTTG1 protein levels in PC and adjacent non-cancerous tissues. A correlation was observed between PTTG1 expression and some clinical characteristics based on the TCGA and IHC data. Univariate and multivariate Cox regressions were used to identify independent prognostic factors. Kaplan-Meier (KM) survival analysis was performed. The co-expressed genes of PTTG1 were determined by integrating online tools, and the enrichment analyses were performed to determine PTTG1-related pathways and hub co-expressed genes. Results: PTTG1 was highly expressed in PC tissues based on the TCGA, GEO, and IHC data. The combined standard mean difference (SMD) values of PTTG1 expression based on TCGA and GEO databases was 1.02 [95% confidence interval (CI): 0.74-1.30]. The area under the curve (AUC) based on the summary receiver operating characteristic (sROC) curve was 0.93 (95% CI: 0.90-0.95). PTTG1 overexpression was remarkably correlated with an inferior overall survival (OS). A total of 367 genes were identified as co-expressed genes of PTTG1 in PC and were mainly involved in the cell cycle pathway. The four identified core genes were CDK1, CCNA2, CDC20, and MAD2L1. Conclusions: The upregulated expression of PTTG1 plays an essential role in PC's progression as a biomarker.

Pituitary tumor transforming gene 1 promotes proliferation and malignant phenotype in osteosarcoma via NF-κB signaling.

BACKGROUND: Pituitary tumor transforming gene (PTTG) is an oncogene reported to be actively promotes tumorigenesis in multiple tumors. Osteosarcoma (OS) is the most common primary osseous sarcoma, however, the functional significance and mechanisms underlying whether and how PTTG1 promotes OS remain largely unknown. METHODS: Here, in our study, PTTG1 levels in clinical samples and cell lines were determined by western blotting and immunohistochemistry. The viability and migratory/invasive potential of OS cells were assessed using Cell Counting Kit-8, colony formation, wound healing, and Transwell assays. The effects of PTTG1 on NF-κB signaling pathways were evaluated both in vivo and in vitro. RESULTS: An abnormally elevated expression of PTTG1was confirmed in human OS tissues and OS cell lines and PTTG1 levels were positively correlated with OS clinicopathological grade. We further showed that knocking down PTTG1 attenuated the viability and migratory/invasive capacity of OS cells (MG63 and HOS-8603). Additionally, the following key mechanistic principle was revealed: knockdown PTTG1-mediated OS tumorgenesis supression was associated with inactivation of the NF-κB pathway. We confirmed these results by additional nonpharmacological intervention and same conclusions were obtained in the context of opposite functional analyses. Furthermore, we also demonstrated that OS cell lines overexpressed PTTG1 showed increased tumorigenesis in athymic nude mice. CONCLUSIONS: To sum up, the present study suggests that PTTG1 is involved in the enhancement of the malignancy and carcinogenesis of OS by regulating NF-κB signaling. Accordingly, PTTG1 likely functions as an oncogene in OS and may represent a potential therapeutic target for this cancer.

PRR11 promotes cell proliferation by regulating PTTG1 through interacting with E2F1 transcription factor in pan-cancer.

The upregulated proline rich 11 (PRR11) plays a critical role in cancer progression. The relevant biological functions of PRR11 in pan-cancer development are not well understood. In the current study, we found that PRR11 was upregulated in 19 cancer types compared with that of normal tissues and high-expressed PRR11 was a predictor of poor prognosis in 10 cancer types by bioinformatics. Then we showed that interfering PRR11 on three cancer cell lines could greatly inhibit cell proliferation and migration and arrest cells to S phase in vivo. Based on RNA-seq, downregulation of PRR11 expression could extremely suppress the expression of PTTG1 and the cell cycle pathway identified by a differentially expressed gene analysis and an enrichment analysis. The expression of PRR11 and PTTG1 was positively correlated in TCGA and independent GEO data sets. Importantly, we revealed that the PRR11 could express itself in the nucleus and interact with E2F1 on the PTTG1 promoter region to increase the expression of PTTG1. Further results indicated that the expression of PTTG1 was also associated with poor prognosis in 10 cancer types, while downregulation of PTTG1 expression could inhibit cancer cell proliferation and migration. Therefore, we found that PRR11 served as an oncogene in pan-cancer and could influence the cell cycle progression through regulating the expression of PTTG1 by interacting with the transcription factor E2F1.

SIRT1 suppresses pituitary tumor progression by downregulating PTTG1 expression.

Although pituitary tumors are among the most common types of brain tumor, the underlying molecular mechanism of this disease remains obscure. To this end, the role of sirtuin 1 (SIRT1) in pituitary tumors was reported. The results of reverse transcription­quantitative PCR and immunohistochemistry revealed that sirtuin 1 (SIRT1) expression was downregulated in the tumor tissues of patients with pituitary tumors. In vitro experiments of the present study demonstrated that SIRT1 upregulation suppressed pituitary tumor cell line growth, while SIRT1 downregulation demonstrated the opposite effect. Additionally, it was determined that the enzymatic activity of SIRT1 was required for its cellular function. A mechanistic experiment determined that SIRT1 negatively regulated pituitary tumor­transforming gene 1 (PTTG1) expression through the deacetylation of histone (H)3 lysine (K)9ac at the promoter region of PTTG1. Moreover, H3K9ac levels at the PTTG1 promoter were determined to be an essential regulatory element for PTTG1 expression. Thus, it was concluded that the SIRT1/H3K9ac/PTTG1 axis contributed to pituitary tumor formation and may represent a potential therapeutic strategy.

Multiple types of noncoding RNA are involved in potential modulation of PTTG1's expression and function in breast cancer.

Breast cancer is a malignant type with morbidity ranking the first of women globally. As widely acknowledged, there exist close links between ncRNA-mRNA axis and breast cancer. In this study, we first overviewed expression and prognostic values of pituitary tumor transforming gene (PTTGs) in breast cancer. Next, two binding miRNAs (miR-186-5p and miR-655-3p) of PTTG1 in breast cancer were identified. Subsequently, several potential upstream ncRNAs of PTTG1-miR-186-5p/miR-655-3p axis in breast cancer were successively screened out, consisting of 11 lncRNAs, 17 circRNAs and 12 pseudogene-derived RNAs. Enrichment analysis for downstream target genes of PTTG1-miR-186-5p/miR-655-3p axis revealed that this axis is associated with TGF-beta signaling and MAPK signaling pathways. Further investigation demonstrated AURKA was one of the most key hub genes. Collectively, we established a potential PTTG1-related ncRNA-mRNA regulatory network in breast cancer.

Association of PTTG1 expression with invasiveness of non-functioning pituitary adenomas.

BACKGROUND: Pituitary tumor transforming gene 1 (PTTG1), paired-like homeodomain 2 (PITX2), and galectin-3 have been widely studied as predictive biomarkers for various tumors and are involved in tumorigenesis and tumor progression. We evaluated the usefulness of PTTG1, PITX2, and galectin-3 as predictive biomarkers for invasive non-functioning pituitary adenomas (NFPAs) by determining the relationship between the expressions of these three proteins and the invasiveness of the NFPAs. We also investigated whether PTTG1, E-cadherin, and Ki-67, which are known to be related to each other, show a correlation with NFPA features. METHODS: A retrospective study was conducted on 87 patients with NPFAs who underwent surgical removal. The NFPAs were classified into three groups based on magnetic resonance imaging findings of suprasellar extension and cavernous sinus invasion. Immunohistochemical staining for PTTG1, PITX2, galectin-3, E-cadherin, and Ki-67 was performed on tissue microarrays. RESULTS: PTTG1 expression showed a statistically significant correlation with the invasiveness of NFPAs, whereas PITX2 and galectin-3 did not have a relationship with the invasiveness of NFPAs. Moreover, there was no association among PTTG1, E-cadherin, and Ki-67 expression. CONCLUSIONS: PTTG1 has the potential to serve as a predictive biomarker for invasive NFPA. Furthermore, this study may serve as a reference for the development of PTTG1-targeted therapeutic agents.

Alteration of Pituitary Tumor Transforming Gene 1 by MicroRNA-186 and 655 Regulates Invasion Ability of Human Oral Squamous Cell Carcinoma.

BACKGROUND: Pituitary tumor-transforming gene 1 (PTTG1) was recently shown to be involved in the progression as well as the metastasis of cancers. However, their expression and function in the invasion of oral squamous cell carcinoma (SCC) remain unclear. METHODS: The expressions of PTTG1 and PTTG1-targeted miRNA in oral SCC cell lines and their invasion capability depended on PTTG1 expression were analyzed by quantitative RT-PCR, Western blots, the transwell insert system and Zymography. RESULTS: Invasion abilities were decreased in oral SCC cells treated with siRNA-PTTG1. When PTTG1 were downregulated in oral SCC cells treated with microRNA-186 and -655 inhibited their invasion abilities via MMP-9 activity. CONCLUSIONS: These results indicate that alteration of expression of PTTG1 in oral SCC cells by newly identified microRNA-186 and -655 can regulate invasion activity. Therefore, these data offer new insights into further understanding PTTG1 function in oral SCC and should provide new strategies for diagnostic markers for oral SCC.

[Correlation of serum PTTG1 expression level with clinicopathological features and prognosis in patients with laryngeal cancer].

Objective:To investigate the correlation between the expression level of serum pituitary tumor transforming gene（PTTG1） and clinicopathological characteristics and prognosis in patients with laryngeal cancer. Method:Enzyme-linked immunosorbent assay was used to detect the expression of serum PTTG1 in 80 patients with laryngeal cancer and 60 patients with vocal cord polyps. The relationship between the clinicopathological characteristics of patients with laryngeal cancer and the expression of serum PTTG1 was analyzed. Cox regression analysis was used to analyze related factors affecting the prognosis of laryngeal cancer. Result:Serum PTTG1 expression level in patients with laryngeal cancer was significantly higher than that in patients with vocal cord polyps, and the difference was statistically significant（P<0.05）. The higher the lymph node metastasis, the higher the tumor TNM stage, and the lower the degree of differentiation, the higher the serum PTTG1 expression level（P<0.05）. In the prognostic survival analysis, univariate analysis showed that lymph node metastasis, tumor TNM stage, degree of differentiation, tumor diameter, and expression of PTTG1 were related to the prognosis of laryngeal cancer（P<0.01）. Cox regression multivariate showed lymph node metastasis（HR=2.651, 95%CI1.452-4.823, P=0.002）, high tumor TNM stage（HR=2.944, 95%CI1.155-6.189, P=0.026）, and low differentiation（HR=1.620, 95%CI1.133-2.169, P=0.003） and high PTTG1 expression（HR=3.511, 95%CI1.432-7.156, P<0.001） were risk factors affecting the prognosis of patients with laryngeal cancer. Conclusion:The expression level of serum PTTG1 may be closely related to the clinicopathological characteristics and prognosis of patients with laryngeal cancer, and its high expression may be one of the indicators of poor prognosis of patients with laryngeal cancer.

Simvastatin Suppresses Human Breast Cancer Cell Invasion by Decreasing the Expression of Pituitary Tumor-Transforming Gene 1.

Statins, or 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, have been widely used to lower cholesterol and prevent cardiovascular diseases. Recent preclinical and clinical studies have shown that statins exert beneficial effects in the management of breast cancer, while the underlying mechanisms remain to be elucidated. Herein, we sought to investigate the effect of statins on the expression of pituitary tumor-transforming gene 1 (PTTG1), a critical gene involved in human breast cancer invasion and metastasis. Our results showed that PTTG1 is highly expressed in malignant Hs578T and MDA-MB-231 breast cancer cell lines as compared with normal or less malignant breast cancer cells. Furthermore, we found that the expression of PTTG1 was markedly suppressed by lipophilic statins, such as simvastatin, fluvastatin, mevastatin, and lovastatin, but not by hydrophilic pravastatin. In a dose and time dependent manner, simvastatin suppressed PTTG1 expression by decreasing PTTG1 mRNA stability in MDA-MB-231 cells. Both siRNA-mediated knockdown of PTTG1 expression and simvastatin treatment markedly inhibited MDA-MB-231 cell invasion, MMP-2 and MMP-9 activity, and the expression of PTTG1 downstream target genes, while ectopic expression of PTTG1 promoted cancer cell invasion, and partly reversed simvastatin-mediated inhibition of cell invasion. Mechanistically, we found that inhibition of PTTG1 expression by simvastatin was reversed by geranylgeranyl pyrophosphate, but not by farnesyl pyrophosphate, suggesting the involvement of geranylgeranyl synthesis in regulating PTTG1 expression. Our results identified statins as novel inhibitors of PTTG1 expression in breast cancer cells and provide mechanistic insights into how simvastatin prevent breast cancer metastasis as observed in recent preclinical and clinical studies.

Identification of critical genes in gastric cancer to predict prognosis using bioinformatics analysis methods.

BACKGROUND: Ranking fourth in the world in tumor incidence and second in cancer-related death worldwide, gastric cancer (GC) is one of the major malignant tumors, and has a very complicated pathogenesis. In the present study, we aimed to identify new biomarkers to predict the survival rate of GC patients. METHODS: The differentially expressed genes (DEGs) between GC tissues and normal stomach tissues were obtained by using GEO2R, and overlapped DEGs were acquired with Venn diagrams. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were conducted with R software. Then, the protein-protein interaction (PPI) of these DEGs was visualized by Cytoscape. Gene Expression Profiling Interactive Analysis (GEPIA) was used to verify the expression differences of hub genes in gastric adenocarcinoma tissues and normal tissues. Overall survival (OS) of hub genes was calculated by Kaplan-Meier plotter. RESULTS: There were a total of 128 consistently expressed genes in the two datasets: 85 upregulated genes were enriched in extra-cellular matrix (ECM)-receptor interaction, protein digestion and absorption, focal adhesion, gastric acid secretion, mineral absorption, systemic lupus erythematosus, amoebiasis, and PI3K-Akt signaling pathway, and 43 downregulated genes were enriched in palate development, blood coagulation, positive regulation of transcription from RNA polymerase II promoter, axonogenesis, receptor internalization, negative regulation of transcription from RNA polymerase II promoter, and in no significant signaling pathways. From the PPI network analyzed by Molecular Complex Detection (MCODE) plug-in, all 27 upregulated genes were selected. Furthermore, to analyze the OS among these genes, Kaplan-Meier analysis was conducted, and 25 genes were associated with remarkably worse survival. For validation in GEPIA, 11 of 25 genes were discovered to be highly expressed in GC tissues compared to normal OS tissues. Furthermore, in the re-analysis of the Database for Annotation, Visualization and Integrated Discovery (DAVID), three genes [G2/miotic-specific cyclin B1 (CCNB1), polo-like kinases 1 (PLK1), and pituitary tumor-transforming gene-1 (PTTG1)] were markedly enriched in the cell cycle pathway, particulary the G1-G1/S phase. CONCLUSIONS: Three remarkably upregulated DEGs with poor prognosis in GC were identified and may serve as new prognostic biomarkers and targets in GC therapy.

STAT3-PTTG11 abrogation inhibits proliferation and induces apoptosis in malignant glioma cells.

Pituitary tumor transforming gene 1 (PTTG11) is abundantly expressed in glioma. Our previous study demonstrated that the downregulation of PTTG11 gene expression significantly inhibited the proliferation, migration and invasion ability, and increased the apoptosis of SHG44 glioma cells. However, the molecular mechanisms that regulate PTTG11 and its actions remain elusive. In the present study, CCK-8 and flow cytometry assays were used to assess the proliferation/viability and apoptosis, respectively, of the human glioma U251 cell line. STAT3-PTTG1 signals were further evaluated by western blotting. The findings of the present study revealed that STAT3 induced PTTG11 expression, which subsequently induced downstream c-Myc and Bcl-2 expression while inhibiting Bax expression, thereby promoting cell viability and inhibiting apoptosis. PTTG11 suppression via siRNA inhibited the viability and increased the apoptosis of glioma cells induced by the STAT3 activator S3I-201. c-Myc and Bcl-2 expression was suppressed by PTTG11 inhibition. The findings of the present study suggest that the STAT3-PTTG11 signaling pathway may play an important role in glioma progression by regulating cell proliferation and apoptosis.

Suppression of PTTG1 inhibits cell angiogenesis, migration and invasion in glioma cells.

Pituitary tumor-transforming gene 1 (PTTG1) has been identified as an oncogene and is overexpressed in many tumor types. However, the role of PTTG1 in glioblastoma (GBM) has not been well characterized, especially in relation to angiogenesis, migration, and invasion. In the present study, our results showed that the expression of PTTG1 was significantly higher in patients with GBM. Bioinformatic analysis showed that angiogenesis and the cell migration-related process were increased in patients with high PTTG1 expression levels; meanwhile, PTTG1 was positively correlated with marker genes of angiogenesis, migration and the evasion of apoptosis. In vitro assays showed that PTTG1 knockdown dramatically suppressed angiogenesis, migration and invasion, and increased the apoptosis of GBM cells. Moreover, our results also showed that silencing PTTG1 suppressed the activity of the TGF-ß/PI3K-AKT-mTOR pathway, which induced tumor deterioration in multiple organs. Overall, our findings indicate that PTTG1 is a glioma malignant factor that promotes angiogenesis, migration, invasion, and the evasion of apoptosis, and these roles may be related to the TGF-ß/PI3K-AKT-mTOR pathway. Thus, the targeted inhibition of PTTG1 might be a novel therapeutic strategy and a potential diagnostic biomarker for GBM-targeted therapies.

Distinct expression pattern and prognostic values of pituitary tumor transforming gene family genes in non-small cell lung cancer.

Members of the pituitary tumor transforming gene (PTTG) family, including PTTG1, PTTG2 and PTTG3P, exhibit pivotal roles in the onset and progression of certain types of human cancer. However, to the best of our knowledge, a systematic study regarding the expression pattern and the prognostic values of PTTG family genes in non-small cell lung cancer (NSCLC) remains to be performed. The expression levels of PTTG family genes in NSCLC were successively determined using the Gene Expression Profiling Interactive Analysis, UALCAN and Oncomine databases. Subsequently, the Kaplan-Meier plotter database was used to assess the prognostic value of the PTTG family genes in patients with NSCLC, and to determine the associations between PTTG expression levels and the prognosis of patients based on different clinicopathological features, including cancer stage, grade, chemotherapy, radiotherapy, lymph node status, smoking history, and sex. PTTG1 was identified to be significantly upregulated in NSCLC in all three databases, whereas PTTG2 and PTTG3P were significantly upregulated in NSCLC in only the UALCAN database. Patients with NSCLC with higher expression levels of the three PTTG genes demonstrated shorter overall survival times. In summary, the results of the present study suggested that increased expression of PTTG family genes may serve as promising prognostic biomarkers for patients with NSCLC.

PTTG1 is involved in TNF-α-related hepatocellular carcinoma via the induction of c-myc.

Hepatocellular carcinoma (HCC) is a malignant disease caused by a variety of factors. However, the genomic and molecular aberrations in HCC are largely unknown. Herein, pituitary tumor transforming gene 1 (PTTG1) was discovered as a potential inflammation-related oncogene in HCC, and its functions and molecular mechanisms were investigated. mRNA expression microarray, real-time polymerase chain reaction (PCR), immunohistochemistry, and western blotting analyses revealed that PTTG1 is upregulated in HCC. Further in vitro and in vivo studies indicated that the proinflammatory cytokine tumor necrosis factor-α (TNF-α) induces PTTG1 expression, and PTTG1 was found to upregulate c-myc, a well-known oncogene. Downregulation of PTTG1 reduced c-myc and proliferating cell nuclear antigen (PCNA) expression and inhibited cell proliferation. Interestingly, inhibition of c-myc by 10058-F4 did not affect PTTG1, which suggests that PTTG1 regulates c-myc expression. Furthermore, PTTG1 expression levels are inversely correlated with HCC patient survival, indicating an independent prognostic biomarker for patients with HCC. Our data demonstrate that PTTG1 is involved in TNF-α-related HCC via c-myc induction and that PTTG1 may be a potential therapeutic target for HCC.

Cancer-Associated Fibroblasts Induce Epithelial-Mesenchymal Transition in Endometrial Cancer Cells by Regulating Pituitary Tumor Transforming Gene.

Cancer-associated fibroblasts (CAFs) play an important role in the development and progression of cancer by inducing epithelial-mesenchymal transition (EMT). In this study, we investigated the role of CAFs in endometrial cancer (EC) cells. We found that the pituitary tumor transforming gene (PTTG) expression was significantly increased in EC cell lines compared to normal human endometrial epithelial cells. Furthermore, CAFs could induce PTTG over-expression and increase EC cell invasion and migration in vitro. In addition, CAFs also induced EMT in EC cells. This study demonstrated that CAFs induced EMT in endometrial cancer cells by regulating PTTG.

The long non-coding RNA PTTG3P promotes growth and metastasis of cervical cancer through PTTG1.

The outgrowth and metastasis of cervical cancer (CC) contribute to its malignancy. Pituitary Tumor Transforming Gene 1 (PTTG1) is upregulated in many types of cancer, and enhances tumor cell growth and metastasis. However, the activation and regulation of PTTG1 in CC, especially by its pseudogene PTTG3P, have not been shown. Here, we detected significantly higher levels of PTTG1 and PTTG3P in the resected CC tissue, compared to the paired adjacent normal cervical tissue. Interestingly, the PTTG3P levels positively correlated with the PTTG1 levels. High PTTG3P levels were associated with poor patients' survival. In vitro, PTTG1 were increased by PTTG3P overexpression, but was inhibited by PTTG3P depletion in CC cells. However, PTTG3P levels were not altered by modulation of PTTG1 in CC cells, suggesting that PTTG3P is upstream of PTTG1. Moreover, PTTG3P increased CC cell growth, likely through CCNB1-mediated increase in cell proliferation, rather than through decrease in cell apoptosis. Furthermore, PTTG3P increased CC cell invasiveness, likely through upregulation of SNAIL and downregulation of E-cadherin. Our work thus suggests that PTTG3P may promote growth and metastasis of CC through PTTG1.

Correlation between narrow-band imaging endoscopy results and hPTTG expression indicated by angiogenensis and its distribution in the initial phase of colorectal adenoma-carcinoma sequence.

The aim of the present study was to investigate the correlation between vascular characteristics under narrow band imaging endoscopy (NBI) and the expression of angiogenic factors of colorectal carcinoma and adenoma, and to evaluate the feasibility and validity of NBI in vivo visualizing angiogenesis. Patients with colorectal polyps, which were pathologically confirmed as early carcinoma, adenoma and hyperplastic polyp, were recruited and examined by NBI. The endoscopic vascular pattern was classified by Showa classification. Immunohistochemical staining was performed by cluster of differentiation (CD34), microvessel density (MVD) and Human Pituitary Tumor-Transforming Gene (hPTTG). The histologic results were compared with the vascular pattern under NBI. Overall, 83 colorectal lesions including 9 intramucosal colorectal carcinomas, 44 adenomas (18 tubular adenomas, 26 tubulovillous adenomas) and 30 hyperplastic polyps were recruited and examined by NBI. A higher proportion (88.6%, 47/53) of intramucosal carcinomas and adenomas were more likely to have the dense pattern (DP) or network pattern (NP), while that of hyperplastic polyps was only 30.0% (9/30). There was an obvious increase in the MVD-CD34 counting from hyperplastic polyps, to adenoma to carcinoma, and a significant difference among the three groups as well. Also, a clear difference can be seen in the expression of hPTTG, which was expressed more in carcinoma than in adenoma and HP group (P < 0.05). Conclusion: NBI might be a useful tool as in vivo visualizing angiogenesis. hPTTG expression in colorectal adenoma and carcinoma is related to angiogenesis.

[Down-regulated PTTG1 expression promotes the senescence of human prostate cancer LNCaP-AI].

OBJECTIVE: To investigate the effect of the down-regulated expression of pituitary tumor-transforming gene 1 (PTTG1) on the senescence of human castration-resistant prostate cancer LNCaP-AI cells. METHODS: Human castration-resistant prostate cancer LNCaP-AI cells were induced in vitro and transfected with siRNA targeting PTTG1 (the siRNA-PTTG1 group), the reagent lip3000 only (the mock group) or siRNA negative control vector (the NC group). All the cells were cultured in fetal bovine serum (FBS) or charcoal-stripped bovine serum (CSS) and counted with the cell counting chamber. The senescence characteristics of the transfected LNCaP-AI cells were examined by senescence-associated ß-galactosidase (SA-ß-Gal) staining, and the expressions of the senescence-related ß-galactosidase-1-like proteins (Glb1), the cyclin-dependent kinase inhibitors p-21CIP1 and p-27Kip1, and the chromatin-regulating heterochromatin protein 1γ (HP1γ) were detected by Western blot. RESULTS: The expression of PTTG1 in the human prostate cancer LNCaP-AI cells was significantly reduced in the siRNA-PTTG1 group compared with those in the mock and NC groups (0.21 ± 0.01 vs 0.56 ± 0.02 and 0.61 ± 0.02, P < 0.05). Culture with FBS markedly increased while that with CSS decreased the number of LNCaP-AI cells transfected with siRNA, but both FBS and CSS enhanced the proliferation of the LNCaP-AI cells in the mock and NC groups. SA-ß-Gal staining revealed that reducing the expression of PTTG1 induced a remarkably higher positive rate of the LNCaP-AI cells in the siRNA-PTTG1 than in the mock and NC groups (ï¼»63.5 ± 2.35ï¼½% vs ï¼»11.3 ± 1.24ï¼½% and ï¼»12.4 ± 1.15ï¼½%, P < 0.05). The siRNA-PTTG1 group, in comparison with the mock and NC groups, showed a significantly down-regulated expression of PTTG1 (0.21 ± 0.01 vs 0.56 ± 0.02 and 0.61 ± 0.02, P < 0.05), but up-regulated expressions of p-21CIP1 (0.32 ± 0.03 vs 0.20 ± 0.02 and 0.21 ± 0.03, P < 0.05), p-27Kip1 (0.38 ± 0.02 vs 0.20 ± 0.03 and 0.22 ± 0.01, P < 0.05), Glb1 (0.24 ± 0.01 vs 0.13 ± 0.01 and 0.15 ± 0.01, P < 0.05), and HP1γ (0.41 ± 0.01 vs 0.26 ± 0.01 and 0.27 ± 0.02, P < 0.05) in the LNCaP-AI cells. CONCLUSIONS: Down-regulated expression of PTTG1 induces senescence of human castration-resistant prostate cancer LNCaP-AI cells.

MicroRNA-329-mediated PTTG1 downregulation inactivates the MAPK signaling pathway to suppress cell proliferation and tumor growth in cholangiocarcinoma.

Cholangiocarcinoma (CCA) is a severe malignancy usually producing a poor prognosis and high mortality rate. MicroRNAs (miRNAs) have been reported in association with CCA; however, the role miR-329 plays in the CCA condition still remains unclear. Therefore, this study was conducted to explore the underlying mechanism of which miR-329 is influencing the progression of CCA. This work studied the differential analysis of the expression chips of CCA obtained from the Gene Expression Omnibus database. Next, to determine both the expression and role of pituitary tumor transforming gene-1 (PTTG1) in CCA, the miRNAs regulating PTTG1 were predicted. In the CCA cells that had been intervened with miR-329 upregulation or inhibition, along with PTTG1 silencing, expression of miR-329, PTTG1, p-p38/p38, p-ERK5/ERK5, proliferating cell nuclear antigen (PCNA), Cyclin D1, Bcl-2-associated X protein (Bax), B-cell CLL/lymphoma 2 (Bcl-2), and caspase-3 were determined. The effects of both miR-329 and PTTG1 on cell proliferation, cell-cycle distribution, and apoptosis were also assayed. The miR-329 was likely to affect the CCA development through regulation of the PTTG1-mediated mitogen-activated protein kinase (MAPK) signaling pathway. The miR-329 targeted PTTG1, leading to inactivation of the MAPK signaling pathway. Upregulation of miR-329 and silencing of PTTG1 inhibited the CCA cell proliferation, induced cell-cycle arrest, and subsequently promoted apoptosis with elevations in Bax, cleaved caspase-3, and total caspase-3, but showed declines in PCNA, Cyclin D1, and Bcl-2. Moreover, miR-329 was also found to suppress the tumor growth by downregulation of PTTG1. To summarize, miR-329 inhibited the expression of PTTG1 to inactivate the MAPK signaling pathway, thus suppressing the CCA progression, thereby providing a therapeutic basis for the CCA treatment.