PTTG1 Expression Research Articles

Multi-omics analysis identifies PTTG1 as a prognostic biomarker associated with immunotherapy and chemotherapy resistance

BackgroundPituitary tumor-transforming gene 1 (PTTG1) is an important gene in tumour development. However, the relevance of PTTG1 in tumour prognosis, immunotherapy response, and medication sensitivity in human pan-cancer has to be determined.MethodsTIMER, GEPIA, the human protein atlas, GEPIA, TISCH2, and cBioportal examined the gene expression, protein expression, prognostic value, and genetic modification landscape of PTTG1 in 33 malignancies based on the TCGA cohort. The association between PTTG1 and tumour immunity, tumour microenvironment, immunotherapy response, and anticancer drug sensitivity was investigated using GSCA, TIDE, and CellMiner CDB. Molecular docking was used to validate the possible chemotherapeutic medicines for PTTG1. Additionally, siRNA-mediated knockdown was employed to confirm the probable role of PTTG1 in paclitaxel-resistant cells.ResultsPTTG1 is overexpressed and associated with poor survival in most tumors. Functional enrichment study revealed that PTTG1 is involved in the cell cycle and DNA replication. A substantial connection between PTTG1 expression and immune cell infiltration points to PTTG1’s possible role in the tumour microenvironment. High PTTG1 expression is associated with tumour immunotherapy resistance. The process could be connected to PTTG1, which mediates T cell exhaustion and promotes cytotoxic T lymphocyte malfunction. Furthermore, PTTG1 was found to be substantially linked with sensitivity to several anticancer medications. Suppressing PTTG1 with siRNA reduced clone formation and migration, implying that PTTG1 may play a role in paclitaxel resistance.ConclusionPTTG1 shows potential as a cancer diagnostic, prognostic, and chemosensitivity marker. Increased PTTG1 expression is linked to resistance to cancer treatment. The mechanism could be linked to PTTG1’s role in promoting cytotoxic T lymphocyte dysfunction and mediating T cell exhaustion. It is feasible to consider PTTG1, which is expressed on Treg and Tprolif cells, as a new therapeutic target for overcoming immunotherapy resistance.

Restoration of ARA metabolic disorders in vascular smooth muscle cells alleviates intimal hyperplasia

Intimal hyperplasia (IH) is an innegligible issue for patients undergoing interventional therapy. The proliferation and migration of vascular smooth muscle cells (VSMCs) induced by platelet-derived growth factor-BB (PDGF-BB) are critical events in the development of IH. While the exact mechanism and effective target for IH needs further investigation. Metabolic disorders of arachidonic acid (ARA) are involved in the occurrence and progression of various diseases. In this study, we found that the expressions of soluble epoxide hydrolase (sEH) and cyclooxygenase-2 (COX-2) were significantly increased in the VSMCs during balloon injury-induced IH. Then, we employed a COX-2/sEH dual inhibitor PTUPB to increase the concentration of epoxyeicosatrienoic acids (EETs) while prevent the release of pro-inflammatory prostaglandins. Results showed that PTUPB treatment significantly reduced neointimal thickening induced by balloon injury in rats in vivo and inhibited PDGF-BB-induced proliferation and migration of VSMCs in vitro. Our results showed that PTUPB may reverse the phenotypic transition of VSMCs by inhibiting Pttg1 expression. In conclusion, we found that the dysfunction of ARA metabolism in VSMCs contributes to IH, and the COX-2/sEH dual inhibitor PTUPB attenuates IH progression by reversing the phenotypic switch in VSMC through the Sirt1/Pttg1 pathway.

GLI1 and PTTG1 expression in colorectal carcinoma patients undergoing radical surgery and their correlation with lymph node metastasis.

Few studies have investigated the expression of GLI1 and PTTG1 in patients undergoing radical surgery for colorectal carcinoma (CRC) and their association with lymph node metastasis (LNM). Therefore, more relevant studies and analyses need to be conducted. To explore GLI1 and PTTG1 expression in patients undergoing radical surgery for CRC and their correlation with LNM. This study selected 103 patients with CRC admitted to our hospital between April 2020 and April 2023. Sample specimens of CRC and adjacent tissues were collected to determine the positive rates and expression levels of GLI1 and PTTG1. The correlation of the two genes with patients' clinicopathological data (e.g., LNM) was explored, and differences in GLI1 and PTTG1 expression between patients with LNM and those without were analyzed. Receiver operating characteristic (ROC) curves were plotted to evaluate the predictive potential of the two genes for LNM in patients with CRC. Significantly higher positive rates and expression levels of GLI1 and PTTG1 were observed in CRC tissue samples compared with adjacent tissues. GLI1 and PTTG1 were strongly linked to LNM in patients undergoing radical surgery for CRC, with higher GLI1 and PTTG1 levels found in patients with LNM than in those without. The areas under the ROC curve of GLI1 and PTTG1 in assessing LNM in patients with CRC were 0.824 and 0.811, respectively. GLI1 and PTTG1 expression was upregulated in patients undergoing radical surgery for CRC and are significantly related to LNM in these patients. Moreover, high GLI1 and PTTG1 expression can indicate LNM in patients with CRC undergoing radical surgery. The expression of both genes has certain diagnostic and therapeutic significance.

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

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. 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. 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. miR-362-3p can inhibit the invasion and proliferation of Cal-27 and HN-30 cells by targeting PTTG1.

Identification of several inflammation-related genes based on bioinformatics and experiments.

Osteoarthritis (OA) is a common disease of elderly individuals, with an unclear pathogenesis and limited treatment options to date. Inflammation occurs prominently in osteoarthritis, thereby making anti-inflammatory treatments promising in clinical outcomes. Therefore, it is of diagnostic and therapeutic significance to explore more inflammatory genes. In this study, appropriate datasets were first acquired through gene set enrichment analysis (GSEA), followed by inflammation-related genes through weighted gene coexpression network analysis (WGCNA). Two machine learning algorithms (random forest-RF and support vector machine-recursive feature elimination, SVM-RFE) were used to capture the hub genes. In addition, two genes negatively associated with inflammation and osteoarthritis were identified. Afterwards, these genes were verified through experiments and network pharmacology. Due to the association between inflammation and many diseases, the expression levels of the above genes in various inflammatory diseases were determined through literature and experiments. Two hub genes closely related to osteoarthritis and inflammation were obtained, namely, lysyl oxidase-like 1 (LOXL1) and pituitary tumour-transforming gene (PTTG1), which were shown to be highly expressed in osteoarthritis according to the literature and experiments. However, the expression levels of receptor expression-enhancing protein (REEP5) and cell division cycle protein 14B (CDC14B) remained unchanged in osteoarthritis. This finding was consistent with our verification from the literature and experiments that some genes were highly expressed in numerous inflammation-related diseases, while REEP5 and CDC14B were almost unchanged. Meanwhile, taking PTTG1 as an example, we found that inhibition of PTTG1 expression could suppress the expression of inflammatory factors and protect the extracellular matrix through the microtubule-associated protein kinase (MAPK) signalling pathway. LOXL1 and PTTG1 were highly expressed in some inflammation-related diseases, while that of REEP5 and CDC14B were almost unchanged. PTTG1 may be a potential target for the treatment of osteoarthritis.

Elevated PTTG1 predicts poor prognosis in kidney renal clear cell carcinoma and correlates with immunity

BackgroundPTTG1 has been reported to be linked with the prognosis and progression of various cancers, including kidney renal clear cell carcinoma (KIRC). In this article, we mainly investigated the associations between prognosis, immunity, and PTTG1 in KIRC patients. MethodWe downloaded transcriptome data from the TCGA-KIRC database. PCR and immunohistochemistry were used, respectively, to validate the expression of PTTG1 in KIRC at the cell line and the protein levels. Survival analyses as well as univariate or multivariate Cox hazard regression analyses were used to prove whether PTTG1 alone could affect the prognosis of KIRC. The most important point was to study the relationship between PTTG1 and immunity. ResultsThe results of the paper revealed that the expression levels of PTTG1 were elevated in KIRC compared with para-cancerous normal tissues, validated by PCR and immunohistochemistry at the cell line and the protein levels (P < 0.05). High PTTG1 expression was related to shorter overall survival (OS) in patients with KIRC (P < 0.05). Through univariate or multivariate regression analysis, PTTG1 was confirmed to be an independent prognostic factor for OS of KIRC (P < 0.05), and its related seven pathways were obtained through gene set enrichment analysis (GSEA; P < 0.05). Moreover, tumor mutational burden (TMB) and immunity were found to be significantly connected with PTTG1 in KIRC (P < 0.05). Correlations between PTTG1 and immunotherapy responses implied that the low-PTTG1 group was more sensitive to immunotherapy (P < 0.05). ConclusionsPTTG1 was closely associated with TMB or immunity, and it had a superior ability to forecast the prognosis of KIRC patients.

Aspirin Mediates Its Antitumoral Effect Through Inhibiting PTTG1 in Pituitary Adenoma

DNA demethylation and inhibitory effects of aspirin on pituitary cell proliferation have been demonstrated. Our aim was to clarify the molecular mechanisms behind the aspirin-related effects in pituitary cells. DNA methylome and whole transcriptome profile were investigated in RC-4B/C and GH3 pituitary cell lines upon aspirin treatment. Effects of aspirin and a demethylation agent, decitabine, were further tested in vitro. PTTG1 expression in 41 human PitNET samples and whole genome gene and protein expression data of 76 PitNET and 34 control samples (available in Gene Expression Omnibus) were evaluated. Aspirin induced global DNA demethylation and consequential transcriptome changes. Overexpression of Tet enzymes and their cofactor Uhrf2 were identified behind the increase of 5-hydroxymethylcytosine (5hmC). Besides cell cycle, proliferation, and migration effects that were validated by functional experiments, aspirin increased Tp53 activity through p53 acetylation and decreased E2f1 activity. Among the p53 controlled genes, Pttg1 and its interacting partners were downregulated upon aspirin treatment by inhibiting Pttg1 promoter activity. 5hmC positively correlated with Tet1-3 and Tp53 expression, and negatively correlated with Pttg1 expression, which was reinforced by the effect of decitabine. Additionally, high overlap (20.15%) was found between aspirin-regulated genes and dysregulated genes in PitNET tissue samples. A novel regulatory network has been revealed, in which aspirin regulated global demethylation, Tp53 activity, and Pttg1 expression along with decreased cell proliferation and migration. 5hmC, a novel tissue biomarker in PitNET, indicated aspirin antitumoral effect in vitro as well. Our findings suggest the potential beneficial effect of aspirin in PitNET.

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.

High expression of pituitary tumor gene family is a predictor for poor prognosis of gastric cancer

Previous studies have suggested that pituitary tumor transforming gene family serves as an oncogene in human cancers. However, the underlying molecular mechanisms of pituitary tumor transforming gene (PTTG) family in gastric cancer are unclear. This study aimed to explore the expression patterns, biological functions, and potential regulatory mechanism of PTTG family in gastric cancer cells. Results showed that the genes of PTTG family were highly expressed in gastric cancer tissues and correlated with low survival outcomes. Further, it was noted that regulation of the PTTG3P expression was associated with miR-129-5p and miR-383-5p. A PTTG3P-miRNA-mRNA regulatory network was established. In addition, results of the functional network analysis revealed that PTTG3P was enriched in transcription and cell signaling pathways. Moreover, results of the LinkedOmics and gene chip technology revealed that PTTG3P was positively correlated with PTTG2, whereas PTTG3P expression was not significantly correlated with PTTG1 expression. In conclusion, these results show that genes of the PTTG family promotes the occurrence and development of gastric cancer with PTTG3P regulating the transcription and cell signaling pathways. PTTG3P has an oncogenic role in gastric cancer by regulating the parental gene PTTG2.

Spindle Cells Oncocytoma and Rathke’s Cyst; A Collision Sellar Tumor– Brief Communication &amp; Case Report

Collision tumors comprising of pituitary adenomas with other sellar neoplasms are rare. Histological examination is necessary since preoperative studies cannot guarantee an accurate diagnosis. A 66-year-old man with headache and progressive visual alterations, MRI showed a sellar tumor that was diagnosed as pituitary adenoma and graduated as HV IIIc. He underwent surgery and two lesions were resected, one on the cavernous sinus and the other one in sellar region. The lesion of the venous sinus corresponds to a cyst covered by a ciliated pseudostratified epithelium that was diagnosed as Rathke's cyst, and the second one was formed by a neoplastic lesion of elongated cells with focal cellular atypia in a sarcomatous pattern, forming fascicles alternating with a pattern formed by medium eosinophilic cells predominantly in elongated cells in a stroma with abundant sinusoids. For immunohistochemistry, the epithelium of the cyst was PTTG-1, cytokeratin 6/8, and chromogranin positive, while the other lesion was positive chromogranin, FSH, LH PTTG-1, TTF-1, while the spindle cells area was positive immunoreaction for PTTG-1, GFAP, S-100, and VIM and weak expression for TTF-1. These histologic and immunohistochemical findings are suggestive of spindle cells oncocytoma and Rathke cyst, is a rare sellar collision tumor. The expression of TTF-1 in the spindle cell oncocytoma with the idea of common histogenesis for pituicytoma and SCOs and raise the possibility of more aggressive growth in SCOs as compared to pituicytoma.

Clinical significance and potential regulatory mechanism of overexpression of pituitary tumor-transforming gene transcription factor in bladder cancer

BackgroundPituitary tumor transforming gene-1 (PTTG1) transcription factor is identified as carcinogenic and associated with tumor invasiveness, but its role in bladder cancer (BLCA) remains obscure. This research is intended to analyze the aberrant expression and clinical significance of PTTG1 in BLCA, explore the relationship between PTTG1 and tumor microenvironment characteristics and predict its potential transcriptional activity in BLCA tissue.MethodsWe compared the expression discrepancy of PTTG1 mRNA in BLCA and normal bladder tissue, using the BLCA transcriptomic datasets from GEO, ArrayExpress, TCGA, and GTEx. In-house immunohistochemical staining was implemented to determine the PTTG1 protein intensity. The prognostic value of PTTG1 was evaluated using the Kaplan-Meier Plotter. CRISPR screen data was utilized to estimate the effect PTTG1 interference has on BLCA cell lines. We predicted the abundance of the immune cells in the BLCA tumor microenvironment using the microenvironment cell populations-counter and ESTIMATE algorithms. Single-cell RNA sequencing data was applied to identify the major cell types in BLCA, and the dynamics of BLCA progression were revealed using pseudotime analysis. PTTG1 target genes were predicted by CistromeDB.ResultsThe elevated expression level of PTTG1 was confirmed in 1037 BLCA samples compared with 127 non-BLCA samples, with a standardized mean difference value of 1.04. Higher PTTG1 expression status exhibited a poorer BLCA prognosis. Moreover, the PTTG1 Chronos genetic effect scores were negative, indicating that PTTG1 silence may inhibit the proliferation and survival of BLCA cells. With PTTG1 mRNA expression level increasing, higher natural killer, cytotoxic lymphocyte, and monocyte lineage cell infiltration levels were observed. A total of four candidate targets containing CHEK2, OCIAD2, UBE2L3, and ZNF367 were determined ultimately.ConclusionsPTTG1 mRNA over-expression may become a potential biomarker for BLCA prognosis. Additionally, PTTG1 may correlate with the BLCA tumor microenvironment and exert transcriptional activity by targeting CHEK2, OCIAD2, UBE2L3, and ZNF367 in BLCA tissue.

Pituitary Tumor-Transforming Gene 1/Delta like Non-Canonical Notch Ligand 1 Signaling in Chronic Liver Diseases

The management of chronic liver diseases (CLDs) remains a challenge, and identifying effective treatments is a major unmet medical need. In the current review we focus on the pituitary tumor transforming gene (PTTG1)/delta like non-canonical notch ligand 1 (DLK1) axis as a potential therapeutic target to attenuate the progression of these pathological conditions. PTTG1 is a proto-oncogene involved in proliferation and metabolism. PTTG1 expression has been related to inflammation, angiogenesis, and fibrogenesis in cancer and experimental fibrosis. On the other hand, DLK1 has been identified as one of the most abundantly expressed PTTG1 targets in adipose tissue and has shown to contribute to hepatic fibrosis by promoting the activation of hepatic stellate cells. Here, we extensively analyze the increasing amount of information pointing to the PTTG1/DLK1 signaling pathway as an important player in the regulation of these disturbances. These data prompted us to hypothesize that activation of the PTTG1/DLK1 axis is a key factor upregulating the tissue remodeling mechanisms characteristic of CLDs. Therefore, disruption of this signaling pathway could be useful in the therapeutic management of CLDs.

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.

The pituitary tumour-transforming gene 1/delta-like homologue 1 pathway plays a key role in liver fibrogenesis.

Background and Aims PTTG1 is almost undetectable in adult livers but is highly expressed in hepatocarcinoma. While little is known about its involvement in liver fibrosis, PTTG1 expression is associated with DLK1. We assessed the role of the PTTG1/DLK1 pathway in fibrosis progression and the potential therapeutic effect of PTTG1 silencing in fibrosis.Methods Pttg1 and Dlk1 were studied in liver and isolated cell populations of control and fibrotic rats and in human liver biopsies. The fibrotic molecular signature was analysed in Pttg1 −/− and Pttg1 +/+ fibrotic mice. Finally, Pttg1 silencing was evaluated in rats as a novel antifibrotic therapy.Results Pttg1 and Dlk1 mRNA selectively increased in fibrotic rats paralleling fibrosis progression. Serum DLK1 concentrations correlated with hepatic collagen content and systemic and portal haemodynamics. Human cirrhotic livers showed greater PTTG1 and DLK1 transcript abundance than non‐cirrhotic, and reduced collagen was observed in Pttg1 Pttg1 −/− mice. The liver fibrotic molecular signature revealed lower expression of genes related to extracellular matrix remodelling including Mmp8 and 9 and Timp4 and greater eotaxin and Mmp13 than fibrotic Pttg1 +/+ mice. Finally, interfering Pttg1 resulted in reduced liver fibrotic area, lower α‐Sma and decreased portal pressure than fibrotic animals. Furthermore, Pttg1 silencing decreased the transcription of Dlk1, collagens I and III, Pdgfrβ, Tgfrβ, Timp1, Timp2 and Mmp2.Conclusions Pttg1/Dlk1 are selectively overexpressed in the cirrhotic liver and participate in ECM turnover regulation. Pttg1 disruption decreases Dlk1 transcription and attenuates collagen deposition. PTTG1/DLK1 signalling is a novel pathway for targeting the progression of liver fibrosis.

Expression of PTTG1 in gastric adenocarcinoma tissues and its relationship with prognosis

Objective: To identify new prognostic markers and therapeutic targets for gastric adenocarcinoma. Methods: The public datasets of gastric adenocarcinoma collected from GEO database (GSE33335 and GSE63089) were downloaded for analysis. There were 70 GC tissues and paired normal tissues in the two profile datasets. Differentially expressed genes (DEGs) between GC tissues and normal stomach tissues were selected by the R software. Protein-protein interaction (PPI) of these DEGs were visualized by the Search Tool for the Retrieval of Interacting Genes (STRING). The key gene sets were analyzed by Cytoscape and Molecular Complex Detection (MCODE). The mRNA and protein expression levels of prognosis related genes identified by public database were confirmed by using GC tissues and paired normal tissues collected from July 2019 to September 2019 in Affiliated Hospital of Nantong University. Results: DEGs were identified in the two datasets by using R software. A total of 128 DEGs were detected, including 85 up-regulated genes (log(2)FC>1.2 and FDR<0.01) and 43 down-regulated genes (log(2)FC<-1.2 and FDR<0.01) in the GC tissues. PPI network model and MCODE model were established by using the Online String tool and Cytoscape software, and 27 key genes were obtained, including 25 genes related with prognosis of GC patients (P<0.05). We identified 14 significant DEGs in GC tissues, including cyclin B1 (CCNB1), polo-like kinase 1 (PLK1) and pituitary-tumor transforming gene (PTTG1), which were significantly enriched in the cell cycle pathway through KEGG pathway enrichment analysis. The positive expression rate of PTTG1 in GC tissues was 68.8% (22/32), significantly higher than 18.8% (6/32) in normal gastric tissues (P<0.05). Conclusions: The expression of PTTG1 is different in GC and gastric tissues, implicates it is the key gene in gastric carcinogenesis. The prognoses of GC patients with higher PTTG1 expression are worse. PTTG1 might participate in the development of gastric adenocarcinoma by regulating cell cycle.

The lncRNA PTTG3P promotes the progression of CRPC via upregulating PTTG1

Overexpression of certain long non-coding RNAs (lncRNAs) promotes the progression of castration-resistant prostate cancer (CRPC). The significance and potential role of the lncRNA designated pituitary tumour-transforming 3, pseudogene (PTTG3P) in CRPC is unknown. We detected PTTG3P expression by qPCR. Upregulated PTTG3P expression was performed to explore the role of PTTG3P in PCa cells resistant to ADT (androgen deprivation therapy). The relationship among PTTG3P, mir-146a-3p and PTTG1 were validated by qPCR, western blot and luciferase assay. PTTG3P levels were significantly increased in the androgen-independent PC cell lines, as well as in CRPC tissues compared with those of the androgen-dependent prostate cancer cell line LNCaP and tumour tissues of patients with hormone-naive prostate cancers. Enforced expression of PTTG3P in androgen-deprived LNCaP cells significantly enhanced survival, clonogenicity, and tumorigenicity. Further, PTTG3P acted as a competing endogenous RNA (ceRNA, natural miRNA sponge) to upregulate PTTG1 expression by competing for mir-146a-3p in the progression to CRPC. Our findings suggest that PTTG3P promotes the resistance of prostate cancer cells to androgen-deprivation therapy via upregulating PTTG1. PTTG3P may therefore represent a potential target for therapy of CRPC.

The Clinical Significance and Potential Molecular Mechanism of PTTG1 in Esophageal Squamous Cell Carcinoma

Esophageal squamous cell carcinoma (ESCC) is the major histological type of esophageal cancers worldwide. Transcription factor PTTG1 was seen highly expressed in a variety of tumors and was related to the degree of tumor differentiation, invasion, and metastasis. However, the clinical significance of PTTG1 had yet to be verified, and the mechanism of abnormal PTTG1 expression in ESCC was not clear. In this study, the comprehensive analysis and evaluation of PTTG1 expression in ESCC were completed by synthesizing in-house immunohistochemistry (IHC), clinical sample tissue RNA-seq (in-house RNA-seq), public high-throughput data, and literature data. We also explored the possible signaling pathways and target genes of PTTG1 in ESCC by combining the target genes of PTTG1 (displayed by ChIP-seq), differentially expressed genes (DEGs) of ESCC, and PTTG1-related genes, revealing the potential molecular mechanism of PTTG1 in ESCC. In the present study, PTTG1 protein and mRNA expression levels in ESCC tissues were all significantly higher than in non-cancerous tissues. The pool standard mean difference (SMD) of the overall PTTG1 expression was 1.17 (95% CI: 0.72–1.62, P < 0.01), and the area under curve (AUC) of the summary receiver operating characteristic (SROC) was 0.86 (95% CI: 0.83–0.89). By combining the target genes displayed by ChIP-seq of PTTG1, DEGs of ESCC, and PTTG1-related genes, it was observed that PTTG1 may interact with these genes through chemokines and cytokine signaling pathways. By constructing a protein–protein interaction (PPI) network and combining ChIP-seq data, we obtained four PTTG1 potential target genes, SPTAN1, SLC25A17, IKBKB, and ERH. The gene expression of PTTG1 had a strong positive correlation with SLC25A17 and ERH, which suggested that PTTG1 might positively regulate the expression of these two genes. In summary, the high expression of PTTG1 may play an important role in the formation of ESCC. These roles may be completed by PTTG1 regulating the downstream target genes SLC25A17 and ERH.

Bisphenol A promotes breast cancer cell proliferation by driving miR-381-3p-PTTG1-dependent cell cycle progression

Bisphenol A (BPA) is a high-production-volume industrial chemical that facilitates the development of breast cancer. However, the molecular mechanism associated with BPA-induced breast cancer cell proliferation and migration remains elusive. In our study, we exposed MCF-7 cells to different concentrations of BPA (0.1, 1 and 10 μM) for 24, 48, or 72 h. We found that BPA exposure significantly promoted MCF-7 cell proliferation and migration but not invasion. To elucidate the mechanisms, the differentially expressed genes between the BPA and control groups were investigated with the Gene Expression Omnibus (GEO) database through GEO2R. Kyoto Encyclopedia of Genes and Genomes (KEGG) and pathway action network analyses demonstrated the important role of the cell cycle pathway in the effects of BPA exposure on MCF-7 cells. Importantly, analysis with the cytoHubba plugin of Cytoscape software coupled with analysis of enriched genes in the cell cycle pathway identified PTTG1 and CDC20 (two hub genes) as key targets associated with BPA-induced MCF-7 cell proliferation and migration. Interestingly, BPA significantly increased the protein expression levels of PTTG1 but not CDC20. Knockdown of PTTG1 inhibited the BPA-induced increase in proliferation and maintained cell cycle progression. In addition, we confirmed that the increased expression of PTTG1 upon BPA exposure was caused by miR-381-3p inhibition. Moreover, we verified that miR-381-3p expression was low and inversely correlated with PTTG1 expression in breast cancer tissues. Together, these findings demonstrate that BPA promotes high PTTG1 expression and alters the cell cycle to enhance MCF-7 cell proliferation by inhibiting miR-381-3p expression.

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.

Expression of pituitary tumor-transforming gene-1 and its pathogenic role in systemic sclerosis

To investigate the expression of tumor-transforming gene-1 (PTTG1) in systemic sclerosis (SSc) and its role in fibrosis. Skin biopsy samples were collected from 21 patients with SSc and 22 patients with healthy skin for detecting the mRNA and protein expressions of PTTG1 using real-time PCR (RT-PCR) and immunohistochemistry, respectively. In cultured primary human dermal fibroblasts, PTTG1 expression was knocked down via RNA interference (siRNA), and the mRNA expression levels of PTTG1 and the fibrosis-related genes α-SMA, COL1A1, COL1A2, and COL3A1 were detected using RT-PCR; the proliferation of the cells was assessed using a real-time cell proliferation detection system. Compared with those in normal skin samples, the mRNA and protein expressions of PTTG1 increased significantly in the skin tissue of patients with SSc (P < 0.05). In cultured primary skin fibroblasts, the expression of PTTG1 mRNA was positively correlated with those of α-SMA (R2=0.8192, P < 0.05), COL1A1 (R2=0.6398, P < 0.05), COL1A2 (R2=0.316, P < 0.05) and COL3A1 mRNAs (R2=0.3727, P < 0.05). Interference of PTTG1 expression significantly inhibited the cell proliferation, obviously lowered the expressions of fibrosis-related genes, and down-regulated the expression of collagen in the fibroblasts. PTTG1 is highly expressed in skin tissues of patients with SSc, and PTTG1 knockdown can reduce the activity of the dermal fibroblasts, suggesting a close correlation of PTTG1 with fibrosis in SSc.