Ask about this productRelated genes to: INTS6 antibody
- Gene:
- INTS6 NIH gene
- Name:
- integrator complex subunit 6
- Previous symbol:
- DDX26
- Synonyms:
- DICE1, HDB, Notchl2, DBI-1, DDX26A, INT6
- Chromosome:
- 13q14.3
- Locus Type:
- gene with protein product
- Date approved:
- 2001-03-30
- Date modifiied:
- 2014-11-18
Related products to: INTS6 antibody
Related articles to: INTS6 antibody
- Hepatocellular carcinoma (HCC) exhibits diverse aetiologies and molecular heterogeneity, with a median 5-year overall survival of <70% due to high recurrence rates following curative-intent surgery. This study investigated the complex tumour microenvironment (TME) in HCC and explored interactions between various cell types and their roles in disease recurrence. - Source: PubMed
Publication date: 2026/02/18
Seshachalam Veerabrahma PSari Ita NToh KaneMajee PrativaChong Shay LSekar KarthikAiderus AzizIdzham KhaireenQi Ong YChong Li YCaldez MatiasShanmugam RaghuvaranYing Dorcas H HLee EsmondToh JiayingLele WuLee Jia Y JZhong GuoruiChew Sin CChen Gao BWu LingyanChung Alexander Y FCheow Peng CKam Juinn HKow Alfred W CLeow Wei QJegannathan NagalakshmiChen KainaBunchaliew Chairatde Villa Vanessa HKoh Peng SBonney GlennGoh Brian K PTam Wai LeongLoo Lit-HsinYeong JoeTergaonkar VinayChow Pierce K H - Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide, with limited therapeutic options and frequent resistance to treatment. The integrator complex subunit 6 (INTS6), a regulator of RNA polymerase II transcription, has emerged as a potential tumor suppressor that modulates Wnt/β-catenin signaling and epithelial-mesenchymal transition (EMT). This study aimed to clarify the role of INTS6 in EMT regulation in HCC and to explore the therapeutic potential of small activating RNA (saRNA)-mediated INTS6 induction. The Cancer Genome Atlas (TCGA) dataset was analyzed to assess the clinical relevance of INTS6 in HCC. Functional studies were conducted using a hepatoma cell line to determine the effects of INTS6 modulation on tumor behavior. Data analysis demonstrated that low INTS6 expression was associated with shorter disease-free survival and poorer prognosis in patients receiving conservative treatment. Experimental suppression of INTS6 increased mesenchymal marker expression, whereas saRNA-mediated induction suppressed these markers. Restoring INTS6 expression reduced cell migration, invasion, and proliferation through G1 cell-cycle arrest and enhanced sensitivity to sorafenib. These findings identify INTS6 as a promising therapeutic target in HCC. saRNA-mediated induction of INTS6 may provide a novel strategy, alone or in combination therapy, to overcome drug resistance and improve clinical outcomes. - Source: PubMed
Publication date: 2025/09/09
Yonezawa SayakaKanno KeishiShiozaki MinamiSugiyama MasanoriIto Masanori - The Integrator complex plays essential roles in RNA polymerase II (RNAPII) transcription termination and RNA processing. Here, we identify INTS6, a subunit of the Integrator complex, as a novel gene associated with neurodevelopmental disorders (NDDs). Through analysis of large NDD cohorts and international collaborations, we identified 23 families harboring monoallelic likely gene-disruptive or de novo missense variants in INTS6. Phenotypic characterization revealed shared features, including language and motor delays, autism, intellectual disability, and sleep disturbances. Using a nervous-system conditional KO (cKO) mouse model, we show that Ints6 deficiency disrupts early neurogenesis, cortical lamination, and synaptic development. Ints6 cKO mice had a thickened ventricular zone/subventricular zone, thinning of the cortical plate, reduced neuronal differentiation, and increased apoptosis in cortical layer 6. Behavioral assessments of heterozygous mice revealed deficits in social novelty preference, spatial memory, and hyperactivity, mirroring phenotypes observed in individuals with INTS6 variants. Molecular analyses further revealed that INTS6 deficiency alters RNAPII dynamics, disrupts transcriptional regulation, and impairs synaptic gene expression. Treatment with a CDK9 inhibitor (CDK9i) reduced RNAPII phosphorylation, thereby limiting its binding to target genes. Notably, CDK9i reversed neurosphere overproliferation and rescued the abnormal dendritic spine phenotype caused by Ints6 deficiency. This work advances understanding of INTS-related NDD pathogenesis and highlights potential therapeutic targets for intervention. - Source: PubMed
Publication date: 2025/09/18
Peng XiaoxiaJia XiangbinWang HanyingChen JingjingZhang XiaoleiTan SenweiDuan XinyuQiu CanHu MengyuanHou HaiyanParenti IlariaKuechler AlmaKaiser Frank JRenck AliciaCaylor RaymondSkinner CindyPeeden JosephCogne BenjaminIsidor BertrandMercier SandraNicolas GaelGuerrot Anne-MarieFaletra FlavioMusante LucianaCohen LiorBergant GaberČuturilo GoranPeterlin BorutSeeley AndreaBachman KristineMartinez-Agosto Julian Avan Ravenswaaij-Arts ConnyBos DennisKim Katherine HBartolomaeus TobiasSchmederer ZeliaAbou Jamra RamiAref-Eshghi ErfanZhao WenjingZou YongyiHu ZhengmaoPan QianLi FaxiangChen GuodongLi JiadaHu ZhangxueXia KunTan JieqiongGuo Hui - The Integrator complex is a set of at least 13 evolutionarily conserved proteins that binds the C-terminal domain of RNA polymerase II to regulate snRNA 3'-end processing and gene expression. Here we show that the Integrator subunit 6 intervenes in the DNA damage response in . We find that upon X-ray radiation, INTS-6 is necessary for RAD-51 foci formation. In addition, CDK-1 Tyr-15 phosphorylation depends on the presence of INTS-6 . This work adds a new piece to elucidate the Integrator complex mechanism of action in DNA repair. - Source: PubMed
Publication date: 2024/11/06
Romero-Aranda CristinaSáenz-Narciso BeatrizGómez-Orte EvaMetola ÁngelaEzcurra BegoñaCalvo OlgaNilsen HildeMiranda-Vizuete AntonioCabello Juan - The biological purpose of Integrator and RNA polymerase II (RNAPII) promoter-proximal pausing remains uncertain. Here, we show that loss of INTS6 in human cells results in increased interaction of RNAPII with proteins that can mediate its dissociation from the DNA template, including the CRL3 E3 ligase, which ubiquitylates CTD serine-phosphorylated RPB1 for degradation. ARMC5-dependent RNAPII ubiquitylation is activated by defects in factors acting at the promoter-proximal pause, including Integrator, DSIF, and capping enzyme. This ARMC5 checkpoint normally curtails a sizeable fraction of RNAPII transcription, and ARMC5 knockout cells produce more uncapped transcripts. When both the Integrator and CRL3 turnover mechanisms are compromised, cell growth ceases and RNAPII with high pausing propensity disperses from the promoter-proximal pause site into the gene body. These data support a model in which CRL3 functions alongside Integrator in a checkpoint mechanism that removes faulty RNAPII complexes at promoter-proximal pause sites to safeguard transcription integrity. - Source: PubMed
Publication date: 2024/11/05
Blears DanielLou JiangmanFong NovaMitter RichardSheridan Ryan MHe DandanDirac-Svejstrup A BarbaraBentley DavidSvejstrup Jesper Q