Ask about this productRelated genes to: Lin28B antibody
- Gene:
- LIN28B NIH gene
- Name:
- lin-28 homolog B
- Previous symbol:
- -
- Synonyms:
- FLJ16517, CSDD2
- Chromosome:
- 6q16.3-q21
- Locus Type:
- gene with protein product
- Date approved:
- 2005-08-22
- Date modifiied:
- 2018-02-13
Related products to: Lin28B antibody
Related articles to: Lin28B antibody
- Epigenetic regulation of chromatin structure is strongly influenced by histone variants and post-translational modifications. The conserved histone variant H2A.Z has been functionally linked to the pioneer factors Sox2 and Oct4, which open chromatin and activate cell fate-specific transcriptional programs. However, the molecular basis of this interaction is not well understood. Here, we combine biochemistry, NMR spectroscopy, and molecular dynamics (MD) simulations to investigate how H2A.Z nucleosome dynamics influence pioneer factor binding. We find that H2A.Z enhances Sox2 and Oct4 association at distinct positions within 601 nucleosomes, correlating with increased DNA accessibility and altered H3 N-terminal tail dynamics. We show that the H3 tail competes with Sox2 for DNA binding and is more efficiently displaced with H2A.Z, while also allowing for unique Sox2-H3 tail interactions. MD simulations reveal that H2A.Z promotes DNA unwrapping, increases inter-gyre spacing, and enhances H3 tail flexibility, while simultaneously reducing contacts with DNA and with the H2A.Z C-terminal tail. This destabilizing effect is DNA-sequence dependent and prominent in the less stable Lin28B nucleosome, which Sox2 appears to substantially reshape. Together, our results suggest that H2A.Z promotes pioneer factor binding by increasing DNA accessibility and reducing histone tail competition, with broad implications for epigenetic regulation and chromatin recognition. - Source: PubMed
Moos Helen KPatel RutikaFlaherty Sophie KLoverde Sharon MNikolova Evgenia N - Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality worldwide, and tumors harboring p53 mutations have limited therapeutic options. Chronic inflammation and microRNA dysregulation are key drivers of NSCLC progression, yet their coordinated therapeutic targeting remains poorly understood. This study aimed to evaluate whether a novel therapeutic combination of colchicine (Col) and rosiglitazone (Rosi) can modulate hsa-miRNA-26a-5p and hsa-miRNA-21-5p and influence IL-6/STAT3/axis-driven oncogenic signaling in NSCLC, particularly under inflammatory conditions. Given the central role of p53 gene in controlling cellular response to therapy, we investigated the role of mutant p53 vs wild-type in response to the individual and combined treatment of Col/Rosi in two NSCLC cell lines, A549 (p53-wild-type) and NCI-H358 (p53-null, transfected with p53-R273H mutant), using WST-1 viability assays, caspase-3 and PARP1 assays, western blotting, and RT-qPCR analysis of key miRNAs. In silico modeling and transcriptomic data from lung adenocarcinoma patients were used to support mechanistic and clinical relevance. In p53-R273H-mutant NCI-H358 cells, the Col/Rosi treatment synergistically reduced viability and induced apoptosis more effectively than either agent alone. This effect was associated with upregulation of the tumor-suppressor hsa-miRNA-26a-5p, suppression of oncogenic hsa-miRNA-21-5p, restoration of PTEN, PDCD4, and LIN28B, and inhibition of the IL-6/STAT3/NF-κB axis, consistent with patient-derived datasets. In contrast, p53-wild-type A549 cells exhibited an antagonistic response. This study identifies a genotype-dependent therapeutic interaction between Col and Rosi and demonstrates that reprogramming of hsa-miRNA-26a-5p and hsa-miRNA-21-5p constitutes a central mechanism underlying their anti-tumor and anti-inflammatory effects in NSCLC, particularly in p53-R273H-mutant NCI-H358 cells compared with p53-wild-type cells. The findings highlight the need for further investigation into the Col/Rosi combination for inflammation-related lung cancer and p53 expression. In vitro studies and bioinformatics analyses suggest a miRNA-associated regulatory mechanism that could guide future research. - Source: PubMed
Publication date: 2026/04/21
Younes NayeraSadek OmaymaSultan Ahmed - Long non-coding RNAs have been found to play a pivotal role in breast cancer, yet the majority of these lncRNAs remain to be thoroughly investigated. This study aimed to explore the role of differentially expressed long non-coding RNAs (lncRNAs) in breast cancer stemness and drug sensitivity. - Source: PubMed
Publication date: 2026/03/23
Zha HuiLi ChaoChen JiaBo HaoHu ZhaolanQin ZailongGuo JieYuan Junbin - Dysregulation of efflux ATP-binding cassette (ABC) transporters often confers multidrug resistance, presenting significant challenges in treating various diseases (eg, hepatocellular carcinoma [HCC]). The let-7-5p microRNAs (miRNAs), commonly downregulated in HCC, have established roles in controlling post-transcriptional gene regulation of ABC transporters (eg, multidrug resistance-associated protein 5 MRP5/ABCC5) and some oncogenes (eg, RNA-binding protein LIN28B). Although previous research has demonstrated the potential of particular let-7-5p isoforms to regulate ABC transporters and inhibit HCC cell viability, the comparative efficacy of let-7-5p isoforms whose sequences differ in several nucleosides is unknown. This study was to compare the effectiveness of 7 major let-7-5p isoforms (let-7a to let-7g) to regulate ABCC5 and LIN28B targets and inhibit HCC cell viability in vitro by using novel bioengineered RNA let-7-5p (BioRNA/let-7-5p) agents. Release of let-7-5p isoforms from individual BioRNA/let-7-5p molecules in Huh7, HepG2, and Hep3B cells was validated. Efficacy of BioRNA/let-7-5p isoforms to repress ABCC5/MRP5 and LIN28B protein levels was found to be target dependent; among them, let-7c and let-7d-5p exhibited broader regulatory efficacy against ABCC5/MRP5, while let-7d-5p emerged as the most potent suppressor of LIN28B, generally in accordance with let-7-5p abundance and target complementarity. By contrast, let-7-5p isoforms showed minimal impact on ABCC2/MRP2 and ABCC4/MRP4 protein levels. In addition, let-7-5p isoforms showed variable efficacy to inhibit the viability of different HCC cells. Together, our studies established the functional differences of let-7-5p isoforms in regulating target gene expression and inhibiting HCC cell viability, providing insights into intrinsic differences of miRNA isoforms to inform rational development of miRNA therapeutics or combination therapy. SIGNIFICANCE STATEMENT: Using novel bioengineered RNA agents, this study established the functional differences of 7 major human let-7-5p isoforms to control target gene expression and hepatocellular carcinoma cell viability in vitro. These findings demonstrate the potential of bioengineered RNA molecules to interrogate post-transcriptional gene regulation mechanisms, highlighting specific let-7-5p isoforms to modulate transporter and oncogene expression toward the development of improved therapies. - Source: PubMed
Publication date: 2026/03/02
Cronin Joseph MTu Mei-JuanWang YimeiYu Ai-Ming - Children with favorable-histology Wilms tumor (FHWT) who relapse or whose tumors show blastemal predominance post-chemotherapy often face poor outcomes. The purpose of this study is to identify mechanisms of chemotherapy resistance in FHWT. We induce a patient-derived xenograft model (KT-47) to develop blastemal predominance after chemotherapy and to become resistant to vincristine, actinomycin-D, and doxorubicin (VAD). Multi-omics analyses reveal chromatin and transcriptional changes, including increased H3K4me3 and decreased H3K27me3 at stem cell and nephrogenesis gene loci. LIN28B is the most upregulated resistance-associated gene, linked to MYCN copy gain/upregulation and chromatin remodeling. ABCB1 expression correlates with interchromosomal enhancer interactions and functions as the mediator of chemotherapy resistance in vitro. These findings are validated in additional Wilms tumor models. Overall, resistance is associated with de-differentiation to a stem-like state and is driven by ABCB1 upregulation, suggesting that therapeutic strategies targeting chromatin regulation and drug efflux may be relevant in therapy-resistant Wilms tumor. - Source: PubMed
Publication date: 2026/03/17
Fleming Andrew MJablonowski Carolyn MJin HongjianZhang SiweiSona SurbhiLee Ha WonDieseldorff Jones Karissa MCheng ChangdeXu BeisiMorton Christopher LWoolard Mary APichavaram PrahalathanGehle Daniel BNatarajan SivaramanKodali KiranPagala VishwajeethHigh Anthony AKumar YogeshBurden StevenValentine VirginiaDaria DeidreHarbour JakeVocelle DanielChang Ti-ChengEaston JohnOlsen Scott RNeale GeoffreyPinto Emilia MRehg Jerold EJanke LauraSantiago TeresaGeorge Rani EMa XiaotuZambetti Gerard PDavidoff Andrew MChen TaoshengWu GangChen XiangYang JunMurphy Andrew J