scholarly journals The functions and prognostic value of Krüppel‐like factors in breast cancer

2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Ke-Yun Zhu ◽  
Yao Tian ◽  
Ying-Xi Li ◽  
Qing-Xiang Meng ◽  
Jie Ge ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Biological Behavior ◽  
Molecular Characteristics ◽  
Clinical Value ◽  
Kegg Pathway Database ◽  
And Migration ◽  
Prognostic Prediction

Abstract Background Krüppel‐like factors (KLFs) are zinc finger proteins which participate in transcriptional gene regulation. Although increasing evidence indicate that KLFs are involved in carcinogenesis and progression, its clinical significance and biological function in breast cancer are still limited. Methods We investigated all the expression of KLFs (KLF1-18) at transcriptional levels by using Oncomine and Gene Expression Profiling Interactive Analysis (GEPIA). The mRNA and protein expression levels of KLFs were also determined by using RT-qPCR and immunohistochemistry, respectively. CBioPortal, GeneMANIA and STRING were used to comprehensive analysis of the molecular characteristics of KLFs. The clinical value of prognostic prediction based on the expression of KLFs was determined by using the KM plotter. The relevant molecular pathways of KLFs were further analyzed by using Gene Set Enrichment Analysis (GSEA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database. Finally, we investigated the effect of KLF2 and KLF15 on biological behavior of breast cancer cells in vitro. Results The expression of KLF2/4/6/8/9/11/15 was significantly down-regulated in breast cancer. The patients with high KLF2, KLF4 or KLF15 expression had a better outcome, while patients with high KLF8 or KLF11 had a poor prognosis. Furthermore, our results showed that KLF2 or KLF15 can be used as a prognostic factor independent on the other KLFs in patients with breast cancer. Overexpression of KLF2 or KLF15 inhibited cell proliferation and migration, and blocked cell cycle at G0/G1 phase, resulting in cell apoptosis. Conclusions KLF2 and KLF15 function as tumor suppressors in breast cancer and are potential biomarkers for prognostic prediction in patients with breast cancer.

The Role of PAX2 in Breast Cancer: A Study Based on Bioinformatics Analysis and in Vitro Validation

2021 ◽  
Author(s):  
Shan Yang ◽  
Wei Gao ◽  
Haoqi Wang ◽  
Xi Zhang ◽  
Yunzhe Mi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Growth ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Mapk Signaling ◽  
Gene Set Enrichment Analysis ◽  
Functional Enrichment ◽  
Migration And Invasion ◽  
Clinical Samples

Abstract Background: Breast cancer (BC) is the most frequently diagnosed cancer in women and is the second most common cancer among newly diagnosed cancers worldwide. Studies have shown that paired box 2 (PAX2) participates in the tumorigenesis of some cancer cells. However, the functions of PAX2 in the BC context are still unclear.Methods: Transcriptome expression profiles and clinicopathological information of BC were download from the TCGA database. Then the expression level and prognostic value in TCGA database were explored. Gene Set Enrichment Analysis (GSEA) and functional enrichment analysis were performed to investigate the functions and pathways of PAX2. Moreover, RT-qPCR was used to determine the expression of PAX2 in BC tissues, and the predictive value of PAX2 in clinical samples was assessed. CCK-8 assay was used to evaluate cell growth. The migration and invasion capacities of cells were assessed by wound healing assay and Transwell assay.Results: PAX2 was up-regulated in the TCGA-BC datasets. GSEA analysis suggested that PAX2 might be involved in the regulation of MAPK signaling pathways and so on. Moreover, PAX2 was overexpressed in BC tissues, and PAX2 expression was associated with menopause. PAX2 deficiency could inhibit the growth, migration, and invasion of BC cells.Conclusion: This study suggested that PAX2 was up-regulated in BC, which inhibited BC cell growth, migration, and invasion. Thus, PAX2 could be a potential therapeutic target for BC.

Down-regulation of DLG2 predicts an unfavorable prognosis and promotes the proliferation and migration of Hepatocellular Carcinoma.

2020 ◽  
Author(s):  
Jiawei Gu ◽  
Runqi Hong ◽  
Gengming Niu ◽  
Zhiqing Hu ◽  
Tao Song ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Enrichment Analysis ◽  
Underlying Mechanism ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Down Regulation ◽  
Normal Tissues ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background Discs large MAGUK scaffold protein 2 (DLG2), a member of the MAGUK family, has been associated with certain tumor suppressing processes. In this study, we aim to identify the prognosis value and specific function of DLG2 in hepatocellular carcinomas (HCCs). Methods Expression of DLG2 in HCCs and adjacent normal tissues (NTs) was analyzed with transcriptomic datasets from the Integrative Molecular Database of Hepatocellular Carcinoma (HCCDB) and immunohistochemical (IHC) staining of a tissue microarray (TMA). Prognostic roles of DLG2 in HCCs were investigated in the TMA cohort and validated in two cohorts from HCCDB. The in vitro activities of DLG2 were investigated in cultured HCC cells with lentiviruses. The underlying mechanism was explored using Gene Set Enrichment Analysis (GSEA) and gene-gene correlation analyses with The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) dataset. Results The expression of DLG2 was significantly decreased in HCCs compared to that in NTs. Down-regulation of DLG2 in HCCs was associated with unfavorable prognosis. Overexpression of DLG2 inhibited, while knockdown of DLG2 prompted proliferation and migration of cultured HCCs. Mechanistically, DLG2 may inhibited cell growth of HCCs by interacting with key molecules that regulate cell cycles. Conclusion DLG2 inhibited HCC progression and may be a novel prognosis biomarker and therapeutic target for HCC.

Pharmacogenomic analysis of HER2 amplified breast cancer treated with preoperative trastuzumab and paclitaxel, 5-fluorouracil, epirubicin, cyclophosphamide (T/FEC) chemotherapy

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 545-545
Author(s):  
F. J. Esteva ◽  
K. Anderson ◽  
F. Lin ◽  
R. Nahta ◽  
J. Mejia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Residual Disease ◽  
Pathologic Complete Response ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Trastuzumab Resistance ◽  
Her2 Receptor ◽  
Gene Set

545 Background: We performed gene expression analysis to identify molecular predictors of resistance to preoperative concomitant trastuzumab and T/FEC chemotherapy. Methods: Pretreatment fine needle aspirations from 21 patients with HER2 amplified, stages II-III breast cancer were available for transcriptional profiling with Affymetrix U133 A chips. Results: Overall pathologic complete response (pCR) rate was 71%. Age, nuclear grade, tumor size, nodal status or quantitative estrogen and HER2 receptor mRNA expression showed no association with response in univariate and multivariate logistic regression. We tested the accuracy of a 30-gene pCR predictor that was previously developed from patients who received T/FEC only preoperative chemotherapy. This predictor was accurate in validation in T/FEC treated patients (n=51) but showed low sensitivity in patients who also received trastuzumab (sensitivity 53% versus 92%). We could not identify any differentially expressed genes between pCR (n=15) and residual disease (RD, n=6) at a false discovery rate (FDR) <90% in the HER2 amplified trastuzumab-treated cases. Hierarchical clustering using the “Perou intrinsic gene set” also failed to separate pCR from RD. Gene Set Enrichment Analysis with 22 genes from trastuzumab-resistant cell lines showed a modest association with RD (FDR=9%). Conclusions: Clinical variables and pharmacogenomic predictors that predict pCR in the absence of trastuzumab are no longer accurate when trastuzumab is included in the treatment. Trastuzumab-resistance associated genes identified in vitro are also associated with resistance in vivo. Support: Ellence Foundation. No significant financial relationships to disclose.

scholarly journals Bioinformatics analysis combined with experiments predicts CENPK as a potential prognostic factor for lung adenocarcinoma

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jiayu Ma ◽  
Xiaochuan Chen ◽  
Mingqiang Lin ◽  
Zhiping Wang ◽  
Yahua Wu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Bioinformatics Analysis ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Biological Behavior ◽  
Tumor Identification

Abstract Background Lung cancer is the most common malignant tumor. Identification of novel diagnostic and prognostic biomarkers for lung cancer is a key research imperative. The role of centromere protein K (CENPK) in cancer is an emerging research hotspot. However, the role of CENPK in the progression of lung adenocarcinoma (LAC) is not well characterized. Methods In this study, we identified CENPK as a potential new gene for lung cancer based on bioinformatics analysis. In addition, in vitro experiments were performed to verify the function of this gene. We investigated the expression of CENPK in LAC by analyses of datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Differential expression analyses, gene ontology (GO) enrichment, Kyoto encyclopedia of genes and genomes (KEGG) analysis, and gene set enrichment analysis (GSEA) were conducted to evaluate the diagnostic and prognostic relevance of CENPK. Then, for evaluating the biological behavior and role of CENPK in lung cancer cells, we did a series of vitro experiments, such as immunohistochemistry analysis, Western blot analysis, CCK8 assay, transwell assay, flow cytometry, and wound healing assay. Results We demonstrated overexpression of CENPK in LAC; in addition, increased expression of CENPK was associated with clinical progression. Moreover, CENPK was found to be an independent risk factor in patients with LAC. Furthermore, we observed activation of CENPK-related signaling pathways in patients with LAC. Conclusions Our findings indicate a potential role of CENPK in promoting tumor proliferation, invasion, and metastasis. It may serve as a novel diagnostic and prognostic biomarker in patients with LAC.

scholarly journals Integrated Bioinformatic Analysis of the Expression and Prognosis of Caveolae-Related Genes in Human Breast Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Yao Tian ◽  
Xiaofeng Liu ◽  
Jing Hu ◽  
Huan Zhang ◽  
Baichuan Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Enrichment Analysis ◽  
Bioinformatic Analysis ◽  
Tumor Stage ◽  
Gene Set Enrichment Analysis ◽  
Advanced Tumor Stage ◽  
Surface Receptors ◽  
Kegg Pathway Database ◽  
Advanced Tumor

Caveolae-related genes, including CAVs that encodes caveolins and CAVINs that encodes caveolae-associated proteins cavins, have been identified for playing significant roles in a variety of biological processes including cholesterol transport and signal transduction, but evidences related to tumorigenesis and cancer progression are not abundant to correlate with clinical characteristics and prognosis of patients with cancer. In this study, we investigated the expression of these genes at transcriptional and translational levels in patients with breast cancer using Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), cBioPortal databases, and immunohistochemistry of the patients in our hospital. Prognosis of patients with breast cancer based on the expressions of CAVs and CAVINs was summarized using Kaplan-Meier Plotter with their correlation to different subtyping. The relevant molecular pathways of these genes were further analyzed using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database and Gene Set Enrichment Analysis (GSEA). Results elucidated that expression levels of CAV1, CAV2, CAVIN1, CAVIN2, and CAVIN3 were significantly lower in breast cancer tissues than in normal samples, while the expression level of CAVIN2 was correlated with advanced tumor stage. Furthermore, investigations on survival of patients with breast cancer indicated outstanding associations between prognosis and CAVIN2 levels, especially for the patients with estrogen receptor positive (ER+) breast cancer. In conclusion, our investigation indicated CAVIN2 is a potential therapeutic target for patients with ER+ breast cancer, which may relate to functions of cancer cell surface receptors and adhesion molecules.

scholarly journals Loss of ferroportin induces memory impairment by promoting ferroptosis in Alzheimer’s disease

2021 ◽  
Author(s):  
Wen-Dai Bao ◽  
Pei Pang ◽  
Xiao-Ting Zhou ◽  
Fan Hu ◽  
Wan Xiong ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Memory Impairment ◽  
Iron Homeostasis ◽  
Critical Role ◽  
Gene Set Enrichment Analysis ◽  
Molecular Characteristics ◽  
Intracellular Iron

AbstractIron homeostasis disturbance has been implicated in Alzheimer’s disease (AD), and excess iron exacerbates oxidative damage and cognitive defects. Ferroptosis is a nonapoptotic form of cell death dependent upon intracellular iron. However, the involvement of ferroptosis in the pathogenesis of AD remains elusive. Here, we report that ferroportin1 (Fpn), the only identified mammalian nonheme iron exporter, was downregulated in the brains of APPswe/PS1dE9 mice as an Alzheimer’s mouse model and Alzheimer’s patients. Genetic deletion of Fpn in principal neurons of the neocortex and hippocampus by breeding Fpnfl/fl mice with NEX-Cre mice led to AD-like hippocampal atrophy and memory deficits. Interestingly, the canonical morphological and molecular characteristics of ferroptosis were observed in both Fpnfl/fl/NEXcre and AD mice. Gene set enrichment analysis (GSEA) of ferroptosis-related RNA-seq data showed that the differentially expressed genes were highly enriched in gene sets associated with AD. Furthermore, administration of specific inhibitors of ferroptosis effectively reduced the neuronal death and memory impairments induced by Aβ aggregation in vitro and in vivo. In addition, restoring Fpn ameliorated ferroptosis and memory impairment in APPswe/PS1dE9 mice. Our study demonstrates the critical role of Fpn and ferroptosis in the progression of AD, thus provides promising therapeutic approaches for this disease.

scholarly journals Controllable Drug Delivery by Na+/K+ ATPase α1 Targeting Peptide Conjugated DSPE-PEG Nanocarriers for Breast Cancer

2021 ◽  
Vol 20 ◽  
pp. 153303382110278
Author(s):  
Yayan Yang ◽  
Qian Feng ◽  
Chuanfeng Ding ◽  
Wei Kang ◽  
Xiufeng Xiao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Delivery ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Click Reaction ◽  
Chemotherapy Drugs ◽  
Targeting Peptide ◽  
And Migration

Although Epirubicin (EPI) is a commonly used anthracycline for the treatment of breast cancer in clinic, the serious side effects limit its long-term administration including myelosuppression and cardiomyopathy. Nanomedicines have been widely utilized as drug delivery vehicles to achieve precise targeting of breast cancer cells. Herein, we prepared a DSPE-PEG nanocarrier conjugated a peptide, which targeted the breast cancer overexpression protein Na+/K+ ATPase α1 (NKA-α1). The nanocarrier encapsulated the EPI and grafted with the NKA-α1 targeting peptide through the click reaction between maleimide and thiol groups. The EPI was slowly released from the nanocarrier after entering the breast cancer cells with the guidance of the targeting NKA-α1 peptide. The precise and controllable delivery and release of the EPI into the breast cancer cells dramatically inhibited the cells proliferation and migration in vitro and suppressed the tumor volume in vivo. These results demonstrate significant prospects for this nanocarrier as a promising platform for numerous chemotherapy drugs.

scholarly journals TNF-α Triggers RIP1/FADD/Caspase-8-Mediated Apoptosis of Astrocytes and RIP3/MLKL-Mediated Necroptosis of Neurons Induced by Angiostrongylus cantonensis Infection

2021 ◽  
Author(s):  
Hongli Zhou ◽  
Minyu Zhou ◽  
Yue Hu ◽  
Yanin Limpanon ◽  
Yubin Ma ◽  
...  
Keyword(s):  
Cell Death ◽  
Enrichment Analysis ◽  
Angiostrongylus Cantonensis ◽  
Gene Set Enrichment Analysis ◽  
Caspase 8 ◽  
Cns Injury ◽  
Vitro Assay ◽  
Tnf Α

AbstractAngiostrongylus cantonensis (AC) can cause severe eosinophilic meningitis or encephalitis in non-permissive hosts accompanied by apoptosis and necroptosis of brain cells. However, the explicit underlying molecular basis of apoptosis and necroptosis upon AC infection has not yet been elucidated. To determine the specific pathways of apoptosis and necroptosis upon AC infection, gene set enrichment analysis (GSEA) and protein–protein interaction (PPI) analysis for gene expression microarray (accession number: GSE159486) of mouse brain infected by AC revealed that TNF-α likely played a central role in the apoptosis and necroptosis in the context of AC infection, which was further confirmed via an in vivo rescue assay after treating with TNF-α inhibitor. The signalling axes involved in apoptosis and necroptosis were investigated via immunoprecipitation and immunoblotting. Immunofluorescence was used to identify the specific cells that underwent apoptosis or necroptosis. The results showed that TNF-α induced apoptosis of astrocytes through the RIP1/FADD/Caspase-8 axis and induced necroptosis of neurons by the RIP3/MLKL signalling pathway. In addition, in vitro assay revealed that TNF-α secretion by microglia increased upon LSA stimulation and caused necroptosis of neurons. The present study provided the first evidence that TNF-α was secreted by microglia stimulated by AC infection, which caused cell death via parallel pathways of astrocyte apoptosis (mediated by the RIP1/FADD/caspase-8 axis) and neuron necroptosis (driven by the RIP3/MLKL complex). Our research comprehensively elucidated the mechanism of cell death after AC infection and provided new insight into targeting TNF-α signalling as a therapeutic strategy for CNS injury.

Transmembrane p24 Trafficking Protein 2 Regulates Inflammation Through the TLR4/NF-κB Signaling Pathway in Lung Adenocarcinoma

2021 ◽  
Author(s):  
Longhua Feng ◽  
Pengjiang Cheng ◽  
Zhengyun Feng ◽  
Xiaoyu Zhang
Keyword(s):  
Lung Adenocarcinoma ◽  
Signaling Pathway ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Inflammatory Factors ◽  
Normal Tissues ◽  
Kaplan Meier ◽  
New Strategy

Abstract Background: To investigate the role of transmembrane p24 trafficking protein 2 (TMED2) in lung adenocarcinoma (LUAD) and determine whether TMED2 knockdown could inhibit LUAD in vitro and in vivo.Methods: TIMER2.0, Kaplan-Meier plotter, gene set enrichment analysis (GSEA), Target Gene, and pan-cancer systems were used to predict the potential function of TMED2. Western blotting and immunohistochemistry were performed to analyze TMED2 expression in different tissues or cell lines. The proliferation, development, and apoptosis of LUAD were observed using a lentivirus-mediated TMED2 knockdown. Bioinformatics and western blot analysis of TMED2 against inflammation via the TLR4/NF-κB signaling pathway were conducted. Results: TMED2 expression in LUAD tumor tissues was higher than that in normal tissues and positively correlated with poor survival in lung cancer and negatively correlated with apoptosis in LUAD. The expression of TMED2 was higher in tumors or HCC827 cells. TMED2 knockdown inhibited LUAD development in vitro and in vivo and increased the levels of inflammatory factors via the TLR4/NF-κB signaling pathway. TMED2 was correlated with TME, immune score, TME-associated immune cells, their target markers, and some mechanisms and pathways, as determined using the TIMER2.0, GO, and KEGG assays.Conclusions: TMED2 may regulate inflammation in LUAD through the TLR4/NF-κB signaling pathway, and enhance the proliferation, development, and prognosis of LUAD by regulating inflammation, which provide a new strategy for treating LUAD by regulating inflammation.

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