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
- Neuropsychiatric symptoms in dementia (NPS) are common and among the most troubling aspects of living with dementia, yet their underlying mechanisms remain unclear. Here, we aimed to identify cerebrospinal fluid (CSF) proteins associated with NPS. - Source: PubMed
Publication date: 2026/06/30
Mei ZhenHoward NicholasHarvey Danielle J Fox EdwardSeyfried Nicholas TWingo Thomas SWingo Aliza P - Skeletal muscle atrophy is driven by an imbalance between anabolic and catabolic signaling pathways, often involving suppression of the PI3K/Akt/mTOR axis. Thyroid Hormones (THs) are key endocrine regulators of skeletal muscle metabolism and adaptation, exerting context-dependent effects that promote either muscle atrophy or hypertrophy. Here, we identify Phosphoinositide-3-kinase interacting protein 1, Pik3ip1, as a critical regulator of TH-dependent muscle homeostasis. Transcriptomic profiling of skeletal muscle from muscle-specific D2 knockout (mD2KO) and TH Receptor knockout (TRKO) mice revealed a catabolic transcriptional program associated with increased Pik3ip1 expression. Consistently, Pik3ip1 expression negatively correlated with TH signaling in vivo and in vitro. Functional studies in C2C12 myotubes showed that Pik3ip1 overexpression suppresses Akt/mTOR signaling, indicating that its induction is sufficient to impair anabolic pathway activation. In vivo, Pik3ip1 expression was rapidly induced during denervation-induced muscle atrophy and remained persistently elevated in mD2KO and TRKO muscles, characterized by altered TH signaling. Sustained Pik3ip1 expression was associated with impaired activation of the Akt/mTOR pathway and enhanced muscle wasting. Conversely, TH treatment reduced Pik3ip1 levels, restored Akt/mTOR signaling, and promoted anabolic responses. Forced Pik3ip1 expression attenuated TH-induced Akt/mTOR phosphorylation, confirming its role as a mediator of TH-dependent anabolic regulation. Collectively, these findings identify Pik3ip1 as a key negative regulator of PI3K/Akt/mTOR signaling in skeletal muscle and establish the TH-Pik3ip1 axis as an important mechanism controlling muscle mass maintenance during atrophic conditions. - Source: PubMed
Publication date: 2026/07/06
Nappi AnnaritaSagliocchi SerenaRestolfer FedericaMiro CaterinaAcampora LuciaAltobelli Giovanna GiuseppinaDentice MonicaCicatiello Annunziata Gaetana - 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