ArticleBMC cancer2017
Integrator complex subunit 6 (INTS6) inhibits hepatocellular carcinoma growth by Wnt pathway and serve as a prognostic marker.
Article in BMC cancer, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 30 citations in OpenAlex.
- Integrator 20th anniversary: a molecular machine indispensable in development and disease.Trends in molecular medicine · 2026Review
- Integrator Complex Subunit 6 Regulates Biological Nature of Hepatocellular Carcinoma by Modulating Epithelial-Mesenchymal Transition.Current issues in molecular biology · 2025Article
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- Exploring RNA binding proteins in hepatocellular carcinoma: insights into mechanisms and therapeutic potential.Journal of experimental & clinical cancer research : CR · 2025Review
- Loosening the Lid on Shoulder Osteoarthritis: How the Transcriptome and Metabolic Syndrome Correlate with End-Stage Disease.International journal of molecular sciences · 2025Article
- INTS7 modulates cell proliferation and apoptosis via promoting cell cycle progression in lung adenocarcinoma.Briefings in functional genomics · 2025Article
- Trophoblast Side-Population Markers are Dysregulated in Preeclampsia and Fetal Growth Restriction.Stem cell reviews and reports · 2024Article
- Expression of signal recognition particle 14 in hepatocellular carcinoma and its relationship with disease progression and patient survival.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2024Article
- Boolean Modeling of Biological Network Applied to Protein-Protein Interaction Network of Autism Patients.Biology · 2024Article
- Unprocessed snRNAs Are a Prognostic Biomarker and Correlate with a Poorer Prognosis in Colorectal Cancer.Cancers · 2024Article
- CRISPR-Cas9 screening identifies INTS3 as an anti-apoptotic RNA-binding protein and therapeutic target for colorectal cancer.iScience · 2024Article
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- Comprehensive analysis based on glycolytic and glutaminolytic pathways signature for predicting prognosis and immunotherapy in ovarian cancer.Journal of Cancer · 2024Article
- Protein-Protein Interaction Network Extraction Using Text Mining Methods Adds Insight into Autism Spectrum Disorder.Biology · 2023Article
- Construction and validation of a novel gene signature for predicting the prognosis of osteosarcoma.Scientific reports · 2022Article
- Microarray and RNA in situ hybridization assay for recurrence risk markers of breast carcinoma and ductal carcinoma in situ: Evidence supporting the use of diverse pathways panels.Journal of cellular biochemistry · 2020Article
- Pseudogene-Derived lncRNAs and Their miRNA Sponging Mechanism in Human Cancer.Frontiers in cell and developmental biology · 2020Review
- Weighted Gene Coexpression Network Analysis Reveals the Dynamic Transcriptome Regulation and Prognostic Biomarkers of Hepatocellular Carcinoma.Evolutionary bioinformatics online · 2020Article
- Angiopoietin-like protein 8 (betatrophin) may inhibit hepatocellular carcinoma through suppressing of the Wnt signaling pathway.Iranian journal of basic medical sciences · 2019Article
- Golgi phosphoprotein 3 (GOLPH3) promotes hepatocellular carcinoma progression by activating mTOR signaling pathway.BMC cancer · 2018Article
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIntegrator complex subunit 6 (INTS6) was found to play a tumour suppressing role in certain types of solid tumours. In this study, we wanted to determine the expression level of INTS6 in hepatocellular carcinoma (HCC) and evaluate its clinical characteristics and mechanisms in HCC patients (Lui and Lu, European Journal of Cancer, 51:S94, 2015).
methodsFirst, we used a microarray analysis to explore the mRNA expression levels in HCC and paired normal liver tissues; second, we used qRT-PCR to measure the INTS6 mRNA levels in a cohort of 50 HCC tissues and adjacent normal liver tissues; third, we used Western blot analyses to detect the INTS6 protein levels in 20 paired HCC and normal liver tissues; fourth, we used immunohistochemistry to determine the INTS6 expression levels in 70 archived paraffin-embedded HCC samples. Finally, we investigated the suppressive function of INTS6 in the Wnt pathway.
resultsHerein, according to the microarray data analysis, the expression levels of INTS6 were dramatically down-regulated in HCC tissues vs. those in normal liver tissues (p<0.05). qRT-PCR and Western blot analyses showed that the INTS6 mRNA and protein expression was significantly down-regulated in tumour tissues compared to the adjacent normal liver tissues (p<0.05). Immunohistochemical assays revealed that decreased INTS6 expression was present in 62.9% (44/70) of HCC patients. Correlation analyses showed that INTS6 expression was significantly correlated with serum alpha-fetoprotein levels (AFP, p =0.004), pathology grade (p =0.005), and tumour recurrence (p =0.04). Kaplan-Meier analysis revealed that patients with low INTS6 expression levels had shorter overall and disease-free survival rates than patients with high INTS6 expression levels (p =0.001 and p =0.001). Multivariate regression analysis indicated that INTS6 was an independent predictor of overall survival and disease-free survival rates. Mechanistically, INTS6 increased WIF-1 expression and then inhibited the Wnt/β-catenin signalling pathway.
conclusionThe results of our study show that down-regulated INTS6 expression is associated with a poorer prognosis in HCC patients. This newly identified INTS6/WIF-1 axis indicates the molecular mechanism of HCC and may represent a therapeutic target in HCC patients.
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