Ask about this productRelated genes to: HCC1 protein
- Gene:
- RBM39 NIH gene
- Name:
- RNA binding motif protein 39
- Previous symbol:
- RNPC2
- Synonyms:
- CC1.3, HCC1, CAPER, fSAP59, CAPERalpha
- Chromosome:
- 20q11.22
- Locus Type:
- gene with protein product
- Date approved:
- 2001-06-21
- Date modifiied:
- 2014-11-19
Related products to: HCC1 protein
Related articles to: HCC1 protein
- Cigarette smoking significantly accelerates the initiation and progression of colorectal cancer (CRC), although the precise molecular mechanisms remain incompletely elucidated. Among tobacco-derived carcinogens, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a key one, which has been demonstrated to enhance the malignant progression of CRC. CUT&RUN-seq and mRNA-seq analyses, along with subsequent validation experiments, reveal that NNK upregulates the expression of the acetyltransferase p300. This, in turn, mediates an increase in H3K27ac modification levels at the ANKHD1 promoter, thereby promoting ANKHD1 expression. Furthermore, high expression of ANKHD1 is significantly correlated with poor prognosis in CRC patients. Phenotypic experiments demonstrate that, compared to p300 overexpression alone, combined p300 overexpression with ANKHD1 knockdown partially suppresses the proliferation and metastatic capacity of CRC cells. This suggests that NNK may promote malignant CRC progression by upregulating the p300-ANKHD1 signaling axis. Further mechanistic investigations indicate that the scaffold protein ANKHD1 directly interacts with RBM39 to facilitate the splicing and expression of MKI67 pre-mRNA, thereby driving the malignant progression of NNK-exposed CRC cells. In summary, this study provides novel insights, proposing that targeting the p300-mediated H3K27ac modification pathway to suppress ANKHD1 expression may represent a promising therapeutic strategy and prognostic marker for CRC patients with a history of smoking. - Source: PubMed
Publication date: 2026/04/28
Jiang MinZhao YutingMa QunDing KunHuang YefeiChen Yansu - Cancer progression relies on dynamic post-transcriptional RNA regulation to enable phenotypic plasticity, immune evasion, and therapeutic resistance. RNA-binding motif (RBM) proteins emerge as pivotal orchestrators of these processes, modulating splicing, mRNA stability, and translation in a context-dependent manner across malignancies. This article provides a narrative mechanistic synthesis of published evidence and does not report original cohort construction or predictive-model development. Here, we review how RBM-driven RNA programs promote proliferative advantages through splicing rewiring, transcript stabilization via m6A modifications, and dual oncogenic/tumor-suppressive roles. We highlight RBM contributions to epithelial-mesenchymal transitions (EMT) and metastatic niche adaptation, including isoform-specific regulation of EMT effectors and metabolic reprogramming. Furthermore, RBMs shape tumor-immune dynamics by triggering innate immune activation through RNA misprocessing, suppressing adaptive immunity through PD-L1 upregulation, and remodeling the immunosuppressive microenvironment via cytokine and metabolic circuits. RBMs also integrate RNA processing with the choice of DNA repair pathways and genotoxic stress responses, underpinning resistance to chemotherapy and radiotherapy. Finally, pharmacological targeting of RBMs, such as RBM39 degradation via molecular glues like indisulam, exploits splicing dependencies to collapse oncogenic states and overcome resistance. These insights position RBMs as therapeutic nodes for precision immuno-oncology, with implications for biomarker-driven strategies in splicing-addicted tumors. - Source: PubMed
Publication date: 2026/04/13
Zhang JunLi YunfengHan HailingZhang Bingya - Lactylation, a newly identified post-translational modification of lactate metabolism, has been implicated in degenerative diseases. However, its roles in intervertebral disc degeneration (IVDD) remain unexplored. This study aimed to identify database- and literature-derived lactylation-associated candidate hub genes (abbreviated as "lactylation-associated candidate hub genes") in IVDD, characterize their biological functions, and validate potential targeted therapeutic compounds. Differential expression analysis of the GSE56081 dataset identified 3305 differentially expressed genes (DEGs). Weighted gene co-expression network analysis (WGCNA) screened IVDD-associated key module genes, which were intersected with 327 known lactylation-associated candidate hub proteins to obtain 42 overlapping genes. Protein-protein interaction (PPI) network analysis (STRING/Cytoscape) identified hub genes, followed by GO/KEGG enrichment, immune infiltration (CIBERSORT), molecular docking, and in vitro validation (CCK-8, LDH, RT-qPCR). Five core lactylation-associated candidate hub genes (RBM39, HNRNPU, SFPQ, HNRNPL, DDX5) may potentially regulate IVDD progression through involvement in RNA metabolism, ferroptosis, HIF-1 signaling, and immune microenvironment remodeling (increased CD8 T cells, Th17 cells, Tregs, macrophages, neutrophils; decreased monocytes, B cells), though direct mechanistic evidence is still needed. Curcumin exhibited strong binding affinity with hub proteins, especially SFPQ (- 7.8 kcal/mol) and regulated their expression in nucleus pulposus cells, maintaining cell viability and reducing cytotoxicity. This study is the first to systematically identify lactylation-associated candidate hub genes that are potentially involved in IVDD pathogenesis via multiple pathways and immune microenvironment modulation. Curcumin shows favorable binding potential with these hub proteins and may serve as a candidate targeted therapeutic agent for IVDD. Our findings provide novel insights into the molecular mechanisms of IVDD and a preliminary basis for guiding the development of lactylation-related precision treatment strategies. - Source: PubMed
Publication date: 2026/04/28
Cai WeiyeLuo YingjinWang JiangpingKong JianLiu YujiangLu BinjieSong BoenLu YueXu BoShen Xiaofeng - Platinum-resistant is a major therapeutic challenge in advanced endometrial cancer (EC), often driven by enhanced DNA damage repair, yet the underlying molecular mechanisms remain incompletely understood. Here, we report that cyclin-dependent kinase 13 (CDK13) is significantly overexpressed in EC tissues, where its high expression correlates with poor patient survival and clinical resistance to platinum-based chemotherapy. Functionally, CDK13 overexpression promoted EC cell proliferation and conferred cisplatin resistance both in vitro and in vivo, whereas its knockdown potentiated cisplatin-induced apoptosis and DNA damage. Mechanistically, through phosphoproteomic analysis, we identified the RNA-binding protein RBM39 as a critical downstream target of CDK13. We demonstrate that CDK13 directly phosphorylates RBM39 at serine 117, and this phosphorylation is essential for CDK13-mediated resistance. Crucially, phosphorylation at Ser117 enhanced the ability of RBM39 to bind and stabilize the mRNA of RAD50, a key DNA repair gene. Post-transcriptional regulation led to an increase in RAD50 protein, which facilitated the repair of DNA damage caused by cisplatin, promoting the survival of cells. The therapeutic relevance of this axis was confirmed in vivo, where dual knockdown of RBM39 and RAD50 synergistically sensitized EC xenografts to cisplatin. Our study first unveils a novel CDK13/RBM39/RAD50 signaling axis that drives platinum resistance in EC by enhancing DNA damage repair via mRNA stabilization, revealing promising therapeutic targets for overcoming chemoresistance in this malignancy. - Source: PubMed
Publication date: 2026/04/15
Yang ChenxiaoZheng XiaoyanSun HaoDu JuntongLuo YoujunWang ChangWu YunlongQu LiyingYuan FangYang Zhan - RAS family proteins, including HRAS, NRAS, and KRAS, are frequently mutated in cancer. Although there has been recent success in designing inhibitors that target oncogenic RAS, they elicit resistance and treating RAS-driven cancer remains difficult. Here, employing a proteomic analysis, we find that multiple spliceosome components are upregulated in the nuclei of cells undergoing RAS-induced senescence. This upregulation depends on RAS signalling and occurs in both senescent preneoplastic and fully transformed cancer cells. Spliceosome components are also highly expressed in preneoplastic and cancerous lesions in human and murine lung, liver, colorectal, and pancreatic cancers. Using siRNA screens, we identify six spliceosome components, including SF3B1 and RBM39, that are essential in cells expressing oncogenic RAS. We find that SF3B1 is required in these cells for maintaining splicing fidelity. By combining transcriptome and splicing analyses with functional screens, we identify the RNA Pol II-associated factor SPT5 as a key mediator of the SF3B1 effects. Importantly, using mouse models of liver cancer, we show that RBM39 and SF3B1 inhibitors are effective in targeting both preneoplastic lesions and aggressive tumours expressing oncogenic RAS. In summary, our study highlights the spliceosome as a promising target for RAS-driven cancers capable of inhibiting both cancer initiation and progression. - Source: PubMed
Publication date: 2026/04/15
Wagner VerenaBousset LauraAscensão-Ferreira MarianaSun BinBarragan Avila José EfrenKaizeler AlexandreMartins-Silva RitaRahbari MohammadFernández-Vaquero MirianHaston ScottTinti MichelePombo JoaquimKhadayate SanjayRoth SusanneSchürch Christian MMartínez-Barbera Juan PedroBahat AnatWee Keng BoonMorton Jennifer PMalek NisarInnes Andrew JVernia SantiagoBarbosa-Morais Nuno LGallage SuchiraHeikenwalder MathiasGil Jesús