ArticleCancer cell international2020
Effect of nicastrin on hepatocellular carcinoma proliferation and apoptosis through PI3K/AKT signalling pathway modulation.
Article in Cancer cell international, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- Prognostic Role of the Activated p-AKT Molecule in Various Hematologic Malignancies and Solid Tumors: A Meta-Analysis.Frontiers in oncology · 2020Pooled it
- Repurposing nirogacestat, a gamma secretase enzyme inhibitor in desmoid tumors.Future oncology (London, England) · 2025Review
- Reduce electrical overload via threaded Chinese acupuncture in nerve electrical therapy.Bioactive materials · 2025Article
- Expression of nicastrin, NICD1, and Hes1 in NCSTN knockout mice: implications for hidradenitis suppurativa, Alzheimer's, and liver cancer.European journal of medical research · 2024Article
- Reliable Hallmarks and Biomarkers of Senescent Lymphocytes.International journal of molecular sciences · 2023Review
- LRP1B suppresses HCC progression through the NCSTN/PI3K/AKT signaling axis and affects doxorubicin resistance.Genes & diseases · 2023Article
- Potential drugs for the treatment of Alzheimer's disease.Pharmacological reports : PR · 2023Review
- Expression analysis elucidates the roles of Nicastrin, Notch4, and Hes1 in prognosis and endocrine-therapy resistance in ER-positive breast cancer patients.Research in pharmaceutical sciences · 2023Article
- The critical role of γ-secretase and its inhibitors in cancer and cancer therapeutics.International journal of biological sciences · 2023Review
- Transcriptome analysis reveals genes associated with stem cell activation by physical exercise in the dentate gyrus of aged p16Ink4a knockout mice.Frontiers in cell and developmental biology · 2023Article
- Proteomics-based investigation of cerebrovascular molecular mechanisms in cerebral amyloid angiopathy by the FFPE-LMD-PCT-SWATH method.Fluids and barriers of the CNS · 2022Article
- PI3K/AKT/mTOR Pathway-Associated Genes Reveal a Putative Prognostic Signature Correlated with Immune Infiltration in Hepatocellular Carcinoma.Disease markers · 2022Article
- Y-box binding protein 1 augments sorafenib resistanceWorld journal of gastroenterology · 2021Article
- LY‑294002 enhances the chemosensitivity of liver cancer to oxaliplatin by blocking the PI3K/AKT/HIF‑1α pathway.Molecular medicine reports · 2021Article
- Effect of astragaloside on diaphragm cell apoptosis in chronic obstructive pulmonary disease.Food science & nutrition · 2020Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIncreasing evidence has proven that the γ-secretase complex plays significant roles in the carcinogenesis of malignancies. However, the independent effect of nicastrin (NCSTN), the largest constituent of the γ-secretase complex, on the progression of hepatocellular carcinoma (HCC) remains to be discovered.
methodsIn our study, we used open online databases, including the Oncomine database, GEPIA and KMPlotter, to analyse the expression of 4 genes and their correlation with prognosis in HCC. NCSTN expression in 60 HCC patients from our centre was determined by immunohistochemical staining and qRT-PCR. The clinical and prognostic significance of NCSTN expression were analysed statistically. Stable Sk-hep1 cell lines with NCSTN overexpression were established using lentivirus-based vectors, and RNAi technology was used to transiently downregulate NCSTN expression in HepG2 cell lines. Cell growth and apoptosis were assessed by using EdU, clone formation, flow cytometry and Western blotting assays.
resultsBioinformatics analysis showed that NCSTN mRNA expression was generally higher in HCC tissues than in normal tissues according to a meta-analysis of 9 HCC datasets, excluding PS-1, PEN-2 and APH-1. Moreover, NCSTN was associated with a poor prognosis in HCC patients from The Cancer Genome Atlas (TCGA). Although the relationship between NCSTN levels and the clinicopathological features of HCC patients was not significant, a survival analysis of HCC patients from TCGA indicated that overall and disease-free survival were significantly associated with NCSTN expression. NCSTN expression in HCC cell lines regulated cell growth and apoptosis in vitro. NCSTN downregulation in HepG2 cells inhibited tumour growth ability in vivo. In addition, NCSTN downregulation in HepG2 cell lines decreased p-PI3K and p-Akt expression, and IGF1, a PI3K/Akt activator, neutralized the effects on PI3K and Akt phosphorylation. Moreover, NCSTN overexpression in Sk-hep1 cells activated the PI3K/Akt signalling pathway, and MK-2206, a PI3K/Akt inhibitor, reversed this activation according to Western blotting analysis.
conclusionsWe suggest that NCSTN serves as an oncogene in HCC by promoting growth and inhibiting apoptosis via the PI3K/Akt pathway, providing a potential novel therapeutic target for HCC treatment.
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