Overexpression of E74-like transformation-specific transcription factor 3 promotes cellular proliferation and predicts poor prognosis in ovarian cancer.
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ABSTRACT:
SUBMITTER: Liu Y
PROVIDER: S-EPMC8358619 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:PurposeThe aim of this study was to investigate the expression of stathmin 1 (STMN1) in ovarian cancer and its effect on prognosis. The effect and mechanism of STMN1 on the proliferation and migration of ovarian cancer cells were also investigated.MethodsExpression of STMN1 was measured by immunohistochemical staining in ovarian cancer tissues. The effects of STMN1 on the proliferation and migration capacity of ovarian cancer were evaluated using Cell Counting Kit-8 (CCK-8) assays, colony formation assays, immunofluorescence staining, wound healing assays, and Transwell assays. Transcription factors were predicted by bioinformatic analysis of TCGA database.ResultsSTMN1 was upregulated in ovarian cancer tissues as compared to paracancerous tissues and associated with shorter overall survival. STMN1 expression significantly correlated with FIGO staging and tumor differentiation (P < 0.05). Furthermore, STMN1 promoted proliferation and migration in ovarian cancer cell lines. Bioinformatic analysis revealed that STMN1 was potentially regulated by E2F transcription factors. Then, we found that E2F1 regulated the expression of STMN1 and affected proliferation.ConclusionSTMN1 is overexpressed in ovarian cancer, and its high expression suggests a poor prognosis. STMN1 promotes the proliferation and migration of ovarian cancer and is regulated by E2F1. Thus, STMN1 may serve as a negative prognostic factor and possible target for the treatment of ovarian cancer patients.
| S-EPMC8849943 | biostudies-literature
Project description:BackgroundProstate cancer (PCa) is one of the most malignant tumors of the male urogenital system. There is an urgent need to identify novel biomarkers for PCa.MethodsIn this study, we evaluated the expression levels of MCM10 in prostate cancer by analyzing public datasets (including The Cancer Genome Atlas and GSE21032). Furthermore, loss of function assays was performed to evaluate the effects of MCM10 on cell proliferation, apoptosis, and colony formation. Furthermore, we performed microarray and bioinformatics analyses to explore the potential mechanisms of MCM10.ResultsIn the present study, we for the first time revealed MCM10 was significantly upregulated in PCa. Moreover, we found increased MCM10 expression was significantly associated with advanced clinical stage and high Gleason score PCa. Kaplan-Meier analysis demonstrated higher MCM10 expression was associated with a poorer patient prognosis in PCa. Furthermore, loss of function assays showed that MCM10 knockdown inhibited cell proliferation and colony formation, but promoted cell apoptosis. Additionally, we performed microarray and bioinformatics analysis and found MCM10 regulated PCa progression by regulating a series of biological processes including cancer, cell death, and apoptosis.ConclusionsThese results suggest that MCM10 may be a potential diagnostic and therapeutic target for PCa.
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Project description:Aberrant expression of critical components of the trans-acting super-enhancers (SE) complex contributes to the continuous and robust transcription of oncogenes in human cancers. Small-molecule inhibitors targeting core-transcriptional components such as transcriptional bromodomain protein 4 (BRD4) and cyclin-dependent kinase 7 (CDK7) have been developed and are currently undergoing preclinical and clinical testing in several malignant cancers. By analysis of TCGA data and clinical specimens, we demonstrated that BRD4 and CDK7 were frequently overexpressed in human HCCs and were associated with the poor prognosis. Shorter survival and poorly differentiated histology were linked to high BRD4 or CDK7 expression levels. Interestingly, co-overexpression of BRD4 and CDK7 was a more unfavorable prognostic factor in HCC. Treatment with JQ1 or THZ1 alone exhibited an inhibitory impact on the proliferation of HCC cells, while JQ1 synergized with THZ1 showed a more pronounced suppression. Concurrently, a combined JQ1 and THZ1 treatment abolished the transcription of oncogenes ETV4, MYC, NFE2L2. Our study suggested that BRD4 and CDK7 coupled can be a valuable biomarker in HCC diagnosis and the combination of JQ1 and THZ1 can be a promising therapeutic treatment against HCC.
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Project description:CD47 is an antiphagocytic signal that cancer cells employ to inhibit macrophage-mediated destruction. CD47 is overexpressed in various human malignancies. However, the expression and functional significance of CD47 in high-grade serous ovarian carcinoma (HGSOC) has not been completely understood. In this study, we reported that CD47 was commonly overexpressed in HGSOC. Higher CD47 expression was significantly correlated with poor prognosis of HGSOC patients. Functional investigations revealed that CD47 overexpression in ovarian cancer cells significantly promoted migration and invasion. Moreover, CD47 induced epithelial-mesenchymal transition (EMT) through modulating E-cadherin and N-cadherin. Our findings suggest that up-regulation of CD47 is correlated with ovarian cancer progression and it might be a potential biomarker for predicting clinical outcomes.
| S-EPMC5489890 | biostudies-other
Project description:Background: Diacylglycerol kinase iota (DGKI) is overexpressed in a variety of cancers and is associated with poor prognosis in colon cancer. This study evaluated the prognostic value of DGKI in gastric cancer (GC) using data from The Cancer Genome Atlas (TCGA). Methods: RNA sequencing results and clinical data of gastric adenoma and adenocarcinoma samples were obtained from the TCGA database (https://portal.gdc.cancer.gov). The Wilcoxon or Kruskal-Wallis test and logistic regression were used to analyze the relationship between DGKI and the clinicopathological characteristics of GC patients. Univariate Cox regression and Kaplan-Meier analysis were used to analyze the clinicopathological characteristics of GC patients and the relationship between DGKI and overall survival time, and multivariate Cox regression analysis was used to identify independent risk factors affecting the prognosis of GC patients. Gene set enrichment analysis (GSEA) was performed using the TCGA dataset. Results: DGKI was overexpressed in gastric tumors and was related to poor prognosis (p = 0.003). Overexpression of DGKI in GC was significantly correlated with high grade (OR = 1.71 for G3 vs. G2), stage (OR = 2.08 for II vs. I) and T classification (OR = 4.64 for T4 vs. T1; OR = 3.99 for T3 vs. T1; OR = 3.37 for T2 vs. T1) (all p <0.05). DGKI (OR = 7.34; p = 0.000) was an independent risk factor affecting the survival of GC patients. The MAPK signaling pathway was differentially enriched with DGKI overexpression. Conclusion: DGKI overexpression may be a potential molecular marker for poor prognosis in GC. The MAPK signaling pathway may be one of the key pathways related to DGKI regulation in GC.
| S-EPMC7358307 | biostudies-literature
Project description:FoxM1 is an oncoprotein that is significantly overexpressed in many malignancies including hepatocellular carcinoma, but its role in intrahepatic cholangiocarcinoma (ICC) remains unclear. This study explores the expression of FoxM1 in human ICC, its relationships with clinical outcomes, and its role in the proliferation, migration, and invasion of ICC in vitro and in vivo. The results show that FoxM1 was markedly elevated in tumor tissues versus the paired peritumoral tissues. Overexpression of FoxM1 was correlated with multiple tumor nodules, tumor size > 5 cm, positive lymph node metastasis and advanced TNM stage. Cox analysis revealed that overexpression of FoxM1 is an independent prognostic indicator for both the overall survival and disease-free survival of ICC patients after hepatectomy. Furthermore, up/downregulation of FoxM1 markedly promoted/inhibited ICC cell proliferation, migration, and invasion in vitro and in vivo. Bioinformatic analysis indicated that overexpression of FoxM1 resulted in the dysregulation of multiple signaling pathways in ICC, and selected components of some key signaling pathways such as c-Myc signaling were confirmed in vitro. In addition, overexpression of FoxM1 enhanced MMP-9 and MMP-2 protein expression in ICC cells. In conclusion, FoxM1 promotes ICC progression and is a reliable predictor of poor prognosis in ICC.
| S-EPMC6326658 | biostudies-literature
Project description:Purpose:Ovarian cancer is a major type of gynecological malignancy which characterized by the chemoresistance, heterogeneity and highly metastasis. However, the mechanism underlying the progression of ovarian cancer remains elusive. Pyruvate dehydrogenase kinase family plays critical roles in tumorigenesis, and PDK4 has been demonstrated to be an oncogene in many types of cancers. The aim of this study was to identify the role of PDK4 in ovarian cancer. Methods:We explored the PDK4 expression according to the public database containing patients with different effect of chemotherapy. Cell proliferation and invasion assays were used to determine the function of PDK4. Mice xenograft experiment was conducted to test the pro-tumorigenesis function of PDK4 in vivo. Cell apoptosis under treatment of chemo drugs was detected by flow cytometry and TUNEL analysis. Spheroid formation assay and CD133+ cell population were used to determine the PDK4-induced stem-like traits. Immunohistochemical staining was performed to test the expression of PDK4 in ovarian cancer tissues, and Kaplan- Meier curve with log-rank test was performed to determine the association between PDK4 expression and ovarian cancer patients' prognosis. Results:Overexpression of PDK4 markedly promoted cell proliferation, invasion and tumor growth in vivo. Furthermore, PDK4 confers cell resistant to chemotherapy-induced apoptosis. Mechanically, we demonstrated that PDK4 induced stem-like traits. Meanwhile, PDK4 expression was significantly evaluated in ovarian cancer tissues compared to that in adjacent non-cancer tissues, and high expression of PDK4 was associated with poor overall survival and progression-free survival of ovarian cancer patients. Conclusion:These results identify a novel role of PDK4 in regulating cell stem-like trait, which directly enhances the cell proliferation, invasion and chemoresistance in ovarian cancer, and targeting PDK4 could be a potential approach for ovarian cancer treatments.
| S-EPMC6307676 | biostudies-literature
Project description:PurposeAccumulating evidence has shown that dysregulation of microRNA-191 (miR-191) is closely associated with tumorigenesis and progression in a wide range of cancers. This study aimed to explore the potential role of miR-191 in esophageal squamous cell carcinoma (ESCC).Materials and methodsmiR-191 expression was assessed in 93 ESCC tissue specimens by real-time polymerase chain reaction, and survival analysis was performed via Kaplan-Meier and Cox regression analyses. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, plate colony-forming, BrdU, and Transwell assays were conducted to observe the effect of miR-191 on ESCC proliferation and invasion. Luciferase reporter and western blot assays were taken to identify target genes of miR-191.ResultsmiR-191 was overexpressed in 93 cases of ESCC, compared with adjacent normal tissues, and miR-191 expression was significantly related to differentiation, depth of invasion, TNM stage, lymph node metastasis, and distant metastasis of tumor. Kaplan-Meier and Cox regression analyses demonstrated that overexpression of miR-191 was an independent and significant predictor of ESCC prognosis. Both gain-of-function and loss-of-function experiments showed that miR-191 promoted ESCC cell proliferation and invasion activities in vitro. Early growth response 1 (EGR1), a tumor suppressor, was predicted as a direct target of miR-191. Luciferase reporter and western blot assays proved that miR-191 reduced EGR1 expression by directly binding its 3' untranslated region. Moreover, EGR1 knockdown by siRNA enhanced ESCC cell growth and invasion.ConclusionOur findings provide specific biological roles of miR-191 in ESCC survival and progression. Targeting the novel miR-191/EGR1 axis represents a potential new therapeutic way to block ESCC development.
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Project description:Background With the feature of destructive and biliary malignancy, intrahepatic cholangiocarcinoma (ICC), presents unclear molecular mechanisms which contributes to typically poor prognosis for patients. Seizure-related 6 homolog-like 2 (SEZ6L2) is a gene that encodes for a seizure-associated protein localized on the cell surface. Thus far, the function of SEZ6L2 in ICC has not been reported. Methods We used data from The Cancer Genome Atlas and the Gene Expression Omnibus to analyze dynamics behind and levels of expression of SEZ6L2 in ICC. Then we used qRT-PCR and Immunohistochemical staining to detect levels of expression of SEZ6L2 and thereby determined the potential clinical significance of this protein in ICC. Results According to qRT-PCR and immunohistochemical analysis results, SEZ6L2 was overexpressed in ICC. Kaplan-Meier and Cox proportional hazard analyses indicated that patients afflicted by ICC with high levels of relative expression of SEZ6L2 have a poorer prognosis and that SEZ6L2 may be an independent prognostic factor which enables to the accurate prediction of overall survival (OS) and disease-free survivals’ (DFS) expected rates. Subcutaneous xenograft models used to explore the role of SEZ6L2 in tumor formation in vivo. The dynamics of the SEZ6L2 gene being promote angiogenesis in cholangiocarcinoma are related to increasing expressive growth factors which include EGF, VEGF, PDGF and the activation of the P38-MAPK pathway. Conclusions Our findings suggest that SEZ6L2 can serve as an advanced biomarker that can be used to accurately predict a patient prognosis and be used as a target for ICC treatment.
| S-EPMC8798643 | biostudies-literature
Project description:Bone morphogenetic proteins (BMPs) both promote and suppress tumorigenesis, and multiple BMP antagonists reportedly contribute to cancer progression. In this study, we demonstrated that the BMP antagonist Chordin-like 2 (CHRDL2) is upregulated in colorectal cancer (CRC) tissues, and that CHRDL2 levels correlate with clinical features of CRC patients, including tumor size, TNM staging, and tumor differentiation. In addition, survival rate and Cox proportional hazards model analyses showed that high CHRDL2 levels correlate with a poor prognosis in CRC. Moreover, CHRDL2 promoted CRC cell proliferation in vitro and in vivo, perhaps through up-regulation of Cyclin D1 and down-regulation of P21. Co-immunoprecipitation assays showed that CHRDL2 bound to BMPs, which inhibited p-Smad1/5, thereby promoting CRC cell proliferation and inhibiting apoptosis. These results suggest CHRDL2 could serve as a biomarker of poor prognosis in CRC, and provide evidence that CHRDL2 acts as an oncogene in human CRC, making it a novel potential therapeutic target.
| S-EPMC5355280 | biostudies-literature