The pituitary tumor-transforming gene 1 (PTTG1) is an oncogene involved in chromosomal segregation, DNA repair, apoptosis, and metabolism. PTTG1 can be used for clinical diagnosis and treatment and is a potential target for oropharyngeal carcinoma. The proliferation and viability of Cal27 and FaDu cells were assessed using the CCK-8 assay. Real-time PCR and western blotting, respectively, were used to analyze the mRNA and protein expression levels of PTTG1 and IFIH1. The interaction between PTTG1 mRNA and the translational regulatory protein IFIH1 was analyzed using RNA pull-down, RNA immunoprecipitation, and luciferase reporter assays. PTTG1 protein was significantly overexpressed in oropharyngeal carcinoma, whereas PTTG1 mRNA was not. We hypothesized that a translation regulatory protein plays a post-transcriptional role in PTTG1. The IFIH1 protein specifically bound to the 42-52 nt region of PTTG1 mRNA, promoted the translation of PTTG1, and promoted the proliferation of oropharyngeal cancer cells. Administration of the PTTG1 inhibitor PHA-848125 and silencing of IFIH1 synergistically decreased the expression of PTTG1, inhibited the proliferation of oropharyngeal cancer cells, and indicated a good prognosis. We found that the IFIH1-PTTG1 axis could regulate the PHA-848125 response and functionally mediate inter-individual oropharyngeal cancer susceptibility and prognosis. This study aimed to confirm the upstream regulatory genes of PTTG1 and further investigate the specific interactions in this signaling pathway, which will provide a new approach for the treatment of oropharyngeal carcinoma.

BACKGROUND: 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.
OBJECTIVE: To explore GLI1 and PTTG1 expression in patients undergoing radical surgery for CRC and their correlation with LNM.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.

This study aimed to clarify the role of pituitary tumor-transforming gene 1 (PTTG1) in proliferation, migration, invasion, and aerobic glycolysis of pancreatic cancer cells, and evaluate the potential of PTTG1 as a therapeutic target. PTTG1 expression in pancreatic cancers was analyzed using the GEPIA databank. In the Panc1 cell with the PTTG1 knockdown or Mia-PaCa2 cells with PTTG1 overexpression, the cell proliferation was evaluated using cell viability curves and colony formation, and wound heal assay and transwell assay were performed to evaluate the migration and invasion, respectively. Furthermore, a western blot was performed to evaluate the expressions of PTTG1, proliferating cell nuclear antigen, E-cadherin, N-cadherin, and c-myc. Meanwhile, the glucose uptake, extracellular acidification rates (ECAR), and oxygen consumption rates (OCR) were analyzed. Our results showed that PTTG1 expression is upregulated in pancreatic cancer, which promoted cell proliferation. Low PTTG1 contributed to higher disease-free survival and overall survival. In Panc1 cell, PTTG1 knockdown resulted in reduced cell viability and colony formation. The migration and invasion abilities of the cells were also reduced in Panc1 with PTTG1 knockdown. Correspondingly, PTTG1 knockdown decreased c-myc expression, glucose uptake, ECAR, and OCR in Panc1 cells. In Mia-PaCa2 cells, PTTG1 overexpression promoted cell proliferation, aerobic glycolysis, and translocation of β-catenin to the nucleus by regulating c-myc. In conclusion, PTTG1 induces proliferation, migration, and invasion, and promotes aerobic glycolysis in pancreatic cancer cells via regulating c-myc, demonstrating the potential of PTTG1 as a therapeutic target.

BACKGROUND: The pituitary tumor-transforming gene 1 (PTTG1), also recognized as securin, plays a crucial role in diverse biological processes, such as restraining sister chromatid segregation, facilitating DNA repair, contributing to organ development, and governing angiogenesis. Additionally, it regulates the expression and secretion of transfer factors. The epigenetic characteristics of PTTG1 suggest its potential in elucidating the progression of malignant tumors in pan-cancer. Nevertheless, the current comprehension of this relationship remains limited, necessitating further comprehensive studies to delve into the underlying pathogenesis.
METHODS: This investigation aimed to explore the potential functions of PTTG1 in pan-cancer by leveraging existing databases, such as TCGA and GTEx. Notably, PTTG1 was overexpressed in nearly all tumors, indicating promising prognostic and diagnostic capabilities. Moreover, the observed correlation between PTTG1 and immune cell infiltration, immune checkpoint genes, tumor mutational burden (TMB), microsatellite instability (MSI), and other immune features suggests its potential utility as a guide for immunotherapy.
RESULTS: The study unveils that the downregulation of PTTG1 expression in neuroblastoma results in reduced cell proliferation and increased apoptosis, substantiating the proposition that PTTG1 could serve as both a prognostic biomarker and a potential target for immunotherapy across various cancer types.
CONCLUSIONS: This study centers on the exploration of the expression and role of PTTG1 in both tumors and the tumor microenvironment (TME), offering valuable insights for the development of cancer therapeutic strategies. These discoveries present potential alternative avenues for addressing clinically resistant cancers.

Pituitary tumor-transforming gene 1 (PTTG1) is overexpressed in various types of tumors and functions as an oncogene; it could also be a potential target in tumor therapy. Meanwhile, the high mortality of pancreatic adenocarcinoma (PAAD) largely depends on the limited effectiveness of therapy. Based on the promising potential of PTTG1 in cancer treatment, we explored the influence of PTTG1 on the treatment of PAAD in this study. The Cancer Genome Atlas Program (TCGA) data showed that higher expression of PTTG1 was associated with higher clinical stages and worse prognosis of pancreatic cancer. In addition, the CCK-8 assay showed that the IC50 of gemcitabine and 5-fluorouracil (5-FU) was increased in BxPC-3-PTTG1high and MIA PaCa-2-PTTG1high cells. The TIDE algorithm indicated that the immune checkpoint blockades\' (ICBs) efficiency is poor in the PTTG1 high group. Furthermore, we found that the efficiency of OAd5 was enhanced in BxPC-3-PTTG1high and MIA PaCa-2-PTTG1high cells and poor in BxPC-3-PTTG1low and MIA PaCa-2-PTTG1low cells. We used the OAd5 expressing GFP for transduction. As a result, the fluorescence intensity was enhanced in BxPC-3-PTTG1high and MIA PaCa-2-PTTG1high cells and decreased in BxPC-3-PTTG1low and MIA PaCa-2-PTTG1low cells 24 h after OAd5 transduction. The fluorescence intensity indicated that PTTG1 increased OAd5 entry. The flow cytometry assay showed that OAd5 receptor CXADR expression was enhanced by PTTG1. PTTG1 failed to further enhance OAd5 transduction in the case of CXADR knockdown. In summary, PTTG1 enhanced OAd5 transduction into pancreatic cancer cells by increasing CXADR expression on the cell surface.

Accidental exposure to phosgene can cause acute lung injury (ALI), characterized by uncontrolled inflammation and impaired lung blood-gas barrier. CD34+CD45+ cells with high pituitary tumor transforming gene 1 (PTTG1) expression were identified around rat pulmonary vessels through single-cell RNA sequencing, and have been shown to attenuate P-ALI by promoting lung vascular barrier repair. As a transcription factor closely related to angiogenesis, whether PTTG1 plays a role in CD34+CD45+ cell repairing the pulmonary vascular barrier in rats with P-ALI remains unclear. This study provided compelling evidence that CD34+CD45+ cells possess endothelial differentiation potential. Rats with P-ALI were intratracheally administered with CD34+CD45+ cells transfected with or without PTTG1-overexpressing and sh-PTTG1 lentivirus. It was found that CD34+CD45+ cells reduced the pulmonary vascular permeability and mitigated the lung inflammation, which could be reversed by knocking down PTTG1. Although PTTG1 overexpression enhanced the ability of CD34+CD45+ cells to attenuate P-ALI, no significant difference was found. PTTG1 was found to regulate the endothelial differentiation of CD34+CD45+ cells. In addition, knocking down of PTTG1 significantly reduced the protein levels of VEGF and bFGF, as well as their receptors, which in turn inhibited the activation of the PI3K/AKT/eNOS signaling pathway in CD34+CD45+ cells. Moreover, LY294002 (PI3K inhibitor) treatment inhibited the endothelial differentiation of CD34+CD45+ cells, while SC79 (AKT activator) yielded the opposite effect. These findings suggest that PTTG1 can promote the endothelial differentiation of CD34+CD45+ cells by activating the VEGF-bFGF/PI3K/AKT/eNOS signaling pathway, leading to the repair of the pulmonary vascular barrier in rats with P-ALI.

UNASSIGNED: PTTG1 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.
UNASSIGNED: We 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.
UNASSIGNED: The 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).
UNASSIGNED: PTTG1 was closely associated with TMB or immunity, and it had a superior ability to forecast the prognosis of KIRC patients.

Heavy drinking is a primary cause of alcoholic liver injury (ALI). Pituitary tumour transforming gene 1 (PTTG1) is involved in the occurrence and development of hepatocellular carcinoma (HCC), which is a well-known inflammation-related cancer with various aetiologies, including alcohol consumption. However, the role of PTTG1 in alcohol-induced liver injury and inflammation is not clear.
Blood samples were collected from patients with acute alcohol intoxication (n = 20) and healthy controls (n = 20). PTTG1 knockout (KO) mice and PTTG1 transgenic (TG) mice were given a single gavage of alcohol (5 g/kg, 50%) to construct the alcohol-induced liver injury.
We found that serum PTTG1 levels were downregulated in acute ALI patients. In addition, acute alcohol administration significantly reduced PTTG1 levels in the serum and liver of mice. Compared to wild-type mice, PTTG1 KO mice had more serious liver injury, which was accompanied by worsened hepatic endoplasmic reticulum (ER) stress and hepatocyte pyroptosis induced by alcohol. Similarly, PTTG1 deficiency exacerbated alcohol-induced cell death in primary mouse hepatocytes and LO2 cells, by increasing hepatic ER stress and pyroptosis. Importantly, TUDCA, an ER stress inhibitor, could blocked alcohol-induced hepatic pyroptosis in PTTG1 knockdown LO2 cells. Finally, overexpression of PTTG1 substantially attenuated alcohol-induced liver injury by reducing ER stress and hepatic pyroptosis in mice.
We demonstrated that PTTG1 participates in ALI and has a protective effect against alcohol-induced hepatic ER stress and pyroptosis.

BACKGROUND: Pituitary 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.
METHODS: We 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.
RESULTS: The 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.
CONCLUSIONS: PTTG1 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.

Tumor-derived extracellular vesicles (EVs) promote ovarian cancer (OC) metastasis by carrying microRNAs (miRs). This study investigated the mechanism of miR-106a-5p carried by OC cell-derived EVs in OC. miR-106a-5p expression in OC tissues and cells was measured. EVs were extracted from SKOV3 cells and normal cells. The internalization of EVs in OC cells was observed. OC cells were treated with SKOV3-EVs or SKOV3-EVs overexpressing miR-106a-5p to detect the proliferation, migration, and invasion. The expression levels of miR-106a-5p, KLF6, and PTTG1 were detected and their binding relationships were identified. Combined experiments were designed to detect the effects of KLF6 and PTTG1 on OC cells. A xenograft tumor experiment was performed to verify the mechanism of EVs-miR-106a-5p and KLF6 in OC metastasis. Consequently, miR-106a-5p was enhanced in OC and correlated with OC metastasis. SKOV3-EVs promoted the proliferation, migration, and invasion of OC cells. Mechanistically, EVs carried miR-106a-5p into other OC cells, inhibited KLF6, reduced the binding of KLF6 to the PTTG1 promoter, and upregulated PTTG1 transcription. Overexpression of KLF6 or silencing of PTTG1 attenuated the promoting effect of EVs-miR-106a-5p on OC cells. EVs-miR-106a-5p facilitated OC metastasis via the KLF6/PTTG1 axis. To conclude, OC cell-derived EVs facilitated the progression and metastasis of OC via the miR-106a-5p/KLF6/PTTG1 axis.