IKBIP promotes tumor development via the akt signaling pathway in esophageal squamous cell carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers worldwide. Inhibitor of kappa B kinase interacting protein (IKBIP) has been reported to promote glioma progression, but its role in other cancers remains unclear. This study aimed to investigate the role of IKBIP and its underlying molecular mechanisms in ESCC. METHODS: The mRNA expression of IKBIP was analyzed using multiple cancer databases. Immunohistochemistry was performed to detect IKBIP protein expression in ESCC tissues and adjacent normal tissues, and Kaplan‒Meier survival and Cox regression analyses were carried out. The effects of IKBIP knockdown (or overexpression) on ESCC cells were detected by cell viability, cell migration, flow cytometry and Western blot assays. LY-294002 was used to validate the activation of the AKT signaling pathway by IKBIP. Finally, the role of IKBIP in ESCC was verified in a xenograft model. RESULTS: Both bioinformatics analysis and immunohistochemistry indicated that IKBIP expression in ESCC tissues was significantly increased and was associated with the prognosis of ESCC patients. In vitro experiments revealed that IKBIP knockdown significantly inhibited the proliferation and migration of ESCC cells, and induced cell apoptosis and G1/S phase arrest. Molecular mechanism results showed that the AKT signaling pathway was further activated after IKBIP overexpression, thereby increasing the proliferation and migration abilities of ESCC cells. In vivo study confirmed that IKBIP promoted the initiation and development of ESCC tumors in mice. CONCLUSIONS: IKBIP plays a tumor-promoting role in ESCC and may serve as a predictive biomarker and a potential therapeutic target for ESCC.

Prognostic value of IKBIP in papillary renal cell carcinoma.

BACKGROUND: I kappa B kinase interacting protein, a highly conserved gene, has rarely been reported in cancer. According to previous study, IKBIP has only been shown to promote malignant progression of glioma. In other malignant tumors, few reports have examined the function of IKBIP, especially in papillary renal cell carcinoma. Therefore, the molecular profiles and clinical prognostic values of the IKBIP in papillary renal cell carcinoma remain undetermined. METHODS: Several bioinformatic platforms and Immunohistochemistry were used to clarify the expression and prognostic values of IKBIP in Papillary renal cell carcinoma. RESULTS: In this study, GEPIA and TIMER platform were used to identify mRNA expression of IKBIP in papillary renal cell carcinoma. And our results revealed that IKBIP mRNA expression was up-regulated in papillary renal cell carcinoma than in its corresponding normal tissues. In addition, high mRNA expression levels of IKBIP were correlated with age, pathological stage, pathological T stage and pathological N stage. Moreover, High IKBIP mRNA expression was negatively correlated with overall survival (OS) and disease-free survival (DFS) in patients of papillary renal cell carcinoma. Besides, Multivariate analysis indicated that IKBIP mRNA expression was an independent prognostic factor for patients of papillary renal cell carcinoma. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed IKBIP co-expressed genes were enriched in homologous recombination, DNA replication, cell cycle, Mismatch repair, Fanconi anemia pathway, P53 signaling pathway and nucleotide excision repair. And Immunohistochemical profile showed that protein expression of IKBIP was higher in papillary renal cell carcinoma than adjacent normal tissue. CONCLUSIONS: Overall, our findings reveled that IKBIP may act as a novel and potential tumor factor to accelerate papillary renal cell carcinoma progression, meanwhile, IKBIP could serve as a promising target for treating papillary renal cell carcinoma.

IKBIP, a novel glioblastoma biomarker, maintains abnormal proliferation of tumor cells by inhibiting the ubiquitination and degradation of CDK4.

Sustained proliferative signaling is a crucial hallmark and therapeutic target in glioblastoma (GBM); however, new intrinsic regulators and their underlying mechanisms remain to be elucidated. In this study, I kappa B kinase interacting protein (IKBIP) was identified to be correlated with the progression of GBM by analysis of The Cancer Genome Atlas (TCGA) data. TCGA database analysis indicated that higher IKBIP expression was associated with high tumor grade and poor prognosis in GBM patients, and these correlations were subsequently validated in clinical samples. IKBIP knockdown induced G1/S arrest by blocking the Cyclin D1/CDK4/CDK6/CDK2 pathway. Our results showed that IKBIP may bind directly to CDK4, a key cell cycle checkpoint protein, and prevent its ubiquitination-mediated degradation in GBM cells. An in vivo study confirmed that IKBIP knockdown strongly suppressed cell proliferation and tumor growth and prolonged survival in a mouse xenograft model established with human GBM cells. In conclusion, IKBIP functions as a novel driver of GBM by binding and stabilizing the CDK4 protein. IKBIP could be a potential therapeutic target in GBM.

IKBIP is a Predictive Biomarker Related to Immunosuppressive Microenvironment in Digestive System Malignancies.

OBJECTIVE: IKBKB-interacting protein (IKBIP) has rarely been reported in tumor research. This study aimed to evaluate IKBIP role in tumor progression. mRNA (messenger ribonucleic acid) expression, clinical characteristics and predictive values of IKBIP were assessed. METHODS: R package "clusterProfiler" was used to examine the potential mechanisms in which IKBIP may involve. Immune cell infiltration and its correlation with IKBIP was also analyzed. We further evaluated IKBIP influence on drug resistance. RESULTS: It was found that IKBIP was overexpressed and related to poorer survival in most types of tumors. IKBIP expression was strongly related to immunosuppressive cells in the TCGA (The Cancer Genome Atlas) pan-cancer samples. These immunosuppressive cells included tumor-related macrophages, tumor-related fibroblasts, and regulatory T cells. Moreover, immunosuppressive genes and immune checkpoints were positively related to IKBIP expression in several tumor types. Furthermore, patients with IKBIP overexpressed did not respond to most anti-cancer medications. It was also found that compared to control group, the number of invasive cells is four times that of IKBIP overexpression group, and the number of clone forming cells is six times that of IKBIP overexpression group. IKBIP overexpression promoted colon cancer cells invasiveness and clonogenesis by Transwell assay and colon formation assay. CONCLUSIONS: According to current findings, IKBIP is a probable oncogene and predictive marker for most of tumor types. High IKBIP expression is associated with tumor immunosuppression.

I kappa B kinase interacting protein as a promising biomarker in pan-cancer: A multi-omics analysis.

Background: Human chromosome 12 contains I kappa B kinase interacting protein (IKBIP) is also commonly known as IKIP. The involvement of IKBIP in the growth of tumors has only been discussed in a small number of publications. Purpose: To explore the role that IKBIP plays in the development of a wide variety of neoplasms, as well as the tumor immunological microenvironment. Methods: UALCAN, HPA, Genotype Tissue Expression, Cancer Genome Maps, and other datasets were used to analyze IKBIP expression. We thoroughly investigated the predictive importance of IKBIP in pan-cancer, clinical traits, and genetic anomalies. We studied whether there is a link between IKBIP and immune-related genes, microsatellite instability (MSI), and the incidence of tumor mutational burden (TMB). The link between immune cell infiltration and IKBIP expression was examined using data on immune cell infiltration from ImmuCellAI, TIMER2, and earlier studies. Finally, gene set enrichment analysis (GSEA) was performed to determine the signaling pathways associated with IKBIP. Results: IKBIP is highly expressed in most cancers and is negatively associated with the prognosis of several major cancer types. Furthermore, IKBIP expression was linked to TMB in 13 cancers and MSI in seven cancers. Additionally, IKBIP is associated with numerous immunological and cancer-promoting pathways. Simultaneously, various cancer types have unique tumor-infiltrating immune cell profiles. Conclusion: IKBIP has the potential to act as a pan-cancer oncogene and is crucial for both carcinogenesis and cancer immunity. Elevated IKBIP expression implies an immunosuppressive environment and may be used as a prognostic biomarker and therapeutic target.

IKBIP might be a potential prognostic biomarker for glioblastoma multiforme.

BACKGROUND: Due to the negative association between inhibitor of nuclear factor-kB kinase-interacting protein (IKBIP) and survival in gliomas, this study aimed to comprehensively analyze the potential function of IKBIP in glioblastoma multiforme (GBM). METHODS: GBM samples were retrieved from The Cancer Genome Atlas and Chinese Glioma Genome Atlas as training and validation cohorts, respectively, and survival and Cox regression analyses were conducted. Based on clinical indicators and IKBIP, three prognostic models were established and then verified using the validation dataset. Infiltrating immune cell analysis and single-sample gene set enrichment analysis were also conducted to explore the underlying mechanisms. Finally, the key findings were validated through molecular biology experiments. RESULTS: Patients in the high IKBIP score group had poorer survival. Based on Cox regression and subgroup analyses, IKBIP was identified as an independent prognostic factor. Among the three models constructed, the model combining the IKBIP signature and clinical features displayed good performance in terms of discrimination, calibration, and model improvement capability in the training cohort. This model was also successfully validated in an external cohort from the CGGA. Further analysis revealed that many immune cells and related pathways were involved in the high-risk group. In vitro experiments revealed that the knockdown of IKBIP inhibited cell invasion and proliferation, and promoted their senescence. CONCLUSIONS: The prognostic value of IKBIP and its positive impact on the invasiveness of GBM were identified, indicating that IKBIP may serve as an underlying target for the treatment of GBM.

V-ATPase subunit C 1 and IKBIP as tandem prospective biomarkers for diabetic nephropathy.

AIMS: The appearance of low-molecular-weight (LMW) protein in the urine indicates any disruption in the structural integrity of the glomerular capillary wall; therefore, the presence of LMW protein may be a potential predictive marker for DN. METHODS: The urine proteomic profiling of T2DM patients (n = 94) and control group (n = 32) was compared by liquid chromatography-tandem mass spectrometry, and the untargeted LMW protein was identified by Progenesis Q1 For Proteomics v4.2. RESULTS: A total of 73 LMW proteins were identified and quantified, of which, 32 proteins were found to be altered significantly (p < 0.05). Further analysis with heat maps identified two potential proteins with the highest folding alterations in urine. V-ATPase subunit C 1 abundance was significantly inversely correlated with microalbumin and significantly decreased in urine, whereas increased IKBIP was positively correlated with microalbumin. The level of those proteins was significantly different among the control, T2DM, and DN groups, implying an association with the progression of DN. CONCLUSIONS: The present findings of our study indicate that the decreasing V-ATPase subunit C 1 together with increasing IKBIP in urine, were found to be closely associated with DN complications and signifying their value as biomarkers for predicting the risk of DN at initial diagnosis.

IKBIP is a novel EMT-related biomarker and predicts poor survival in glioma.

BACKGROUND: In cancer, kappa B-interacting protein (IKBIP) has rarely been reported. This study aimed at investigating its expression pattern and biological function in brain glioma at the transcriptional level. METHODS: We selected 301 glioma patients with microarray data from CGGA database and 697 glioma patients with RNAseq data from TCGA database. Transcriptional data and clinical data of 998 samples were analyzed. Statistical analysis and figure generating were performed with R language. RESULTS: We found that IKBIP expression showed positive correlation with WHO grade of glioma. IKBIP was increased in isocitrate dehydrogenase (IDH) wild type and mesenchymal molecular subtype of glioma. Gene ontology analysis demonstrated that IKBIP was profoundly associated with extracellular matrix organization, cell-substrate adhesion and response to wounding in both pan-glioma and glioblastoma. Subsequent gene set enrichment analysis revealed that IKBIP was particularly correlated with epithelial-to-mesenchymal transition (EMT). To further elucidate the relationship between IKBIP and EMT, we performed gene set variation analysis to screen the EMT-related signaling pathways and found that IKBIP expression was significantly associated with PI3K/AKT, hypoxia and TGF-ß pathway. Moreover, IKBIP expression was found to be synergistic with key biomarkers of EMT, especially with N-cadherin, vimentin, snail, slug and TWIST1. Finally, higher IKBIP indicated significantly shorter survival for glioma patients. CONCLUSIONS: IKBIP was associated with more aggressive phenotypes of gliomas. Furthermore, IKBIP was significantly involved in EMT and could serve as an independent prognosticator in glioma.

hsa_circ_0072389, hsa_circ_0072386, hsa_circ_0008621, hsa_circ_0072387, and hsa_circ_0072391 aggravate glioma via miR-338-5p/IKBIP.

Glioma is a primary intracranial tumor with high morbidity and mortality. We acquired miR-338-5p, which suppresses the development of glioma, from the GEO and CGGA databases. In addition, we predicted that hsa_circ_0072389, hsa_circ_0072386, hsa_circ_0008621, hsa_circ_0072387, and hsa_circ_0072391 could relieve the silencing of IKBIP by miR-338-5p. By analyzing genes related to IKBIP expression, possible pathways affecting glioma were identified. This study provides new ideas for investigating multiple circRNAs in ceRNAs.