Ask about this productRelated genes to: PIK3IP1 Blocking Peptide
- Gene:
- PIK3IP1 NIH gene
- Name:
- phosphoinositide-3-kinase interacting protein 1
- Previous symbol:
- -
- Synonyms:
- HGFL, MGC17330, TrIP
- Chromosome:
- 22q12.2
- Locus Type:
- gene with protein product
- Date approved:
- 2007-04-13
- Date modifiied:
- 2019-03-01
Related products to: PIK3IP1 Blocking Peptide
Related articles to: PIK3IP1 Blocking Peptide
- Glioblastoma (GBM) is a highly aggressive brain tumor characterized by rapid proliferation, diffuse invasion, and robust immunosuppression. Although excessive aerobic glycolysis and lactate accumulation are known to contribute to an immunosuppressive microenvironment, the upstream transcriptional mechanisms connecting metabolic reprogramming and immunotherapy resistance in GBM remain unclear. By integrating transcriptomic profiling, chromatin immunoprecipitation sequencing, and metabolic analysis with gene perturbation experiments, we identified a regulatory axis comprising RFX7 and its downstream target PIK3IP1. In GBM tissues, RFX7 expression was reduced due to promoter hypermethylation. Restoration of RFX7 enhanced PIK3IP1 expression, suppressed PI3K/AKT activation, and inhibited malignant progression in GBM. Loss of PIK3IP1 increased lactate production and histone H4K12 lactylation (H4K12la), coinciding with upregulation of PD-L1 and CSF1 and enhanced tumor immunosuppressive features. Pharmacological inhibition of lactate production with Stiripentol reduced H4K12la level, intracranial tumor growth, and immunosuppressive cell infiltration, while improving survival and response to immune checkpoint based therapy in experimental models. These findings identify an upstream transcriptional pathway linking lactate metabolism, histone lactylation, and immune suppression in GBM. Targeting the RFX7-PIK3IP1 axis provides a mechanistic rationale for metabolic-immune modulation in therapy, addressing an aspect that has remained insufficiently understood in GBM immune resistance. - Source: PubMed
Publication date: 2026/05/28
Han LiyingZhou JinpengZhu GangChen FanLi LeiyangCui WenxingSun FangFeng TianZhang YueWang QiangMa ShuoyaoGuo ChengxuanZhang ZiwenWang KaiWang JiahuiWang LiangboLi WencongYuan ChenyiLiu HaixiaoWang LiangQu Yan - Gastric cancer (GC) remains one of the leading causes of cancer-related mortality worldwide, with malignant metastasis being a major determinant of patient prognosis. The metastatic process involves a number of phenotypic alterations, including enhanced invasive and migratory capacities. The growing availability of unbiased transcriptomic data has facilitated the identification of metastasis-associated molecular biomarkers and has enabled the exploration of their underlying mechanisms, with the aim of identifying novel therapeutic targets. In the present study, differential expression analysis was performed using The Cancer Genome Atlas Stomach Adenocarcinoma dataset to identify genes associated with malignant metastasis in GC. Prognostic signature genes were subsequently identified using Least Absolute Shrinkage and Selection Operator and Cox regression analyses. Western blotting, wound healing and Transwell assays were performed to investigate the association between gene expression, PI3K/AKT signaling activity, and GC cell invasion and migration. The interaction between uroplakin 1B (UPK1B) and PI3K inhibitor interacting protein 1 (PIK3IP1) was experimentally validated. A set of prognostic signature genes associated with the malignant metastasis of GC was identified, among which UPK1B and chorionic gonadotropin subunit β-5 were demonstrated to be independent predictors of a poor outcome. Notably, UPK1B was validated as an independent biomarker of poor prognosis and a potential therapeutic target in GC. Functional experiments revealed that UPK1B interacted with PIK3IP1 and attenuated the inhibitory effect of PIK3IP1 on the PI3K/AKT signaling pathway, thereby enhancing GC cell invasion and migration. In addition, caudal-related homeobox transcription factor 2 (CDX2) was identified as the transcriptional repressor of UPK1B. The present study delineated prognostic signature genes associated with malignant metastasis of GC. Among them, UPK1B served a pivotal role in regulating GC cell invasion and migration via the CDX2-UPK1B-PIK3IP1-PI3K/AKT axis. These findings provide novel insights into the molecular mechanisms underlying GC metastasis, and highlight UPK1B as a promising biomarker and therapeutic target for future GC therapies. - Source: PubMed
Publication date: 2026/05/08
Zhong ShaodongZhang HengHuang Jin - Apigenin, a naturally occurring flavonoid with low toxicity, exhibits anticancer activity, yet its effects on microRNAs (miRNAs) and downstream gene networks in esophageal squamous cell carcinoma (ESCC) remain unclear. Here, we evaluated apigenin's antitumor effects in TE-1 and Eca-109 cells, assessing proliferation, apoptosis, colony formation, and invasion. Differentially expressed miRNAs were identified via small RNA sequencing, and candidate target genes were predicted, annotated using GO and KEGG analyses, and validated by qRT-PCR, revealing miRNA-mediated regulatory mechanisms underlying apigenin's inhibitory effects in ESCC. Apigenin markedly suppressed cell proliferation, clonogenic growth, wound closure, and invasive capacity, while promoting apoptosis in a dose-dependent manner. In TE-1 cells, apigenin upregulated hsa-let-7c-3p, hsa-miR-374c-3p, hsa-miR-3177-3p hsa-miR-4454, and hsa-miR-4728-3p, while downregulating hsa-miR-573, hsa-miR-548az-5p, hsa-miR-33b-5p, hsa-miR-4479, and hsa-miR-3198. Correspondingly, tumor-associated target genes including , , , and were upregulated, whereas , , , and were suppressed. In Eca-109 cells, apigenin altered the expression of distinct miRNAs, including the upregulation of hsa-miR-891-5p, hsa-miR-3170, hsa-miR-4421, and hsa-miR-675-5p and the downregulation of hsa-miR-153, hsa-miR-3188, and hsa-miR-4435, thereby modulating key oncogenic targets such as , , and . Functional enrichment analyses indicated that apigenin-regulated genes are involved in multiple cancer-related pathways across cytoplasmic and nuclear compartments. Overall, these results suggest that apigenin suppresses ESCC progression via coordinated miRNA-mRNA regulation, highlighting its potential as a therapeutic agent. - Source: PubMed
Publication date: 2026/02/28
Amjad NoumanMajid MuhammadSun ZhaojianBasnet RajeshRasool KashafWu LinpingLi Zhiyuan - This study aimed to initially characterize the effects of GANT61, a Hedgehog (Hh) signaling pathway inhibitor, on the biological behaviors of ALK-positive anaplastic large cell lymphoma (ALK + ALCL) cell lines and explore its underlying mechanisms. Cell proliferation was determined by CCK-8 assays. Cell cycle distribution and apoptotic rates were assessed by flow cytometry. Differential gene analysis and pathway enrichment studies were conducted using datasets from the GEO database with R packages. Protein expression levels of apoptosis-related markers (Bcl-2, Bax, caspase-3, cleaved caspase-3) and signaling molecules (Gli1, PIK3IP1, Akt, phosphorylated Akt) were quantitatively examined by western blotting. Corresponding mRNA levels were quantified by qRT-PCR. GANT61 treatment inhibited proliferation in a dose- and time-dependent manner, induced cell cycle arrest, and promoted apoptosis in ALK + ALCL cell lines. Notably, PIK3IP1 expression was markedly reduced compared with normal lymphocyte controls, while GAS1 expression showed significant upregulation in ALK + ALCL cell lines. Gene Set Enrichment Analysis (GSEA) demonstrated significant enrichment of the PI3K/Akt and Hh signaling pathways. Mechanistically, GANT61 upregulated PIK3IP1 while downregulating both Gli1 protein level and Akt phosphorylation. The Gli-targeting agent GANT61 may inhibit ALK + ALCL cell growth, trigger cell cycle arrest and induce apoptosis through Gli1 inhibition, potentially leading to PIK3IP1 upregulation and subsequent attenuation of PI3K/Akt pathway activity. These findings indicate that the Hh-PIK3IP1-Akt signaling axis may participate in ALK + ALCL tumorigenesis, showing that conventional target drugs can be employed for ALK + ALCL treatment. - Source: PubMed
Publication date: 2026/01/23
Chen HongyuanGao JingjingLi ChuntuanHan YanLiu ShengquanZhu Xiongpeng - To date, there is still a lack of studies focusing on the interactions between tobacco smoking, epigenetic modifications, and heart failure (HF) risk. - Source: PubMed
Publication date: 2026/01/13
Song Zheng-QiWang Bo-XiangZhou Zhi-BoWu Sheng-KeSun Yi-HanChen Yi-He