RNA-binding motif protein 47 (RBM47) is an evolutionarily conserved multifunctional RNA-binding protein. It mediates post-transcriptional regulation through C-to-U RNA editing, alternative splicing, and messenger RNA (mRNA) stability control. Preclinical evidence indicates that RBM47 exhibits context-dependent, dual effects in human disease. In breast cancer (BC), colorectal cancer (CRC), renal cell carcinoma (RCC), papillary thyroid carcinoma (PTC), and non-small cell lung cancer (NSCLC), experimental studies suggest that RBM47 exerts tumor-suppressive activity through the inhibition of the Wnt/β-catenin, phosphoinositide 3-kinase (PI3K)-AKT, and nuclear factor erythroid 2-related factor 2 (Nrf2) pathways. Conversely, in glioma and pancreatic cancer (PC), cell and animal models indicate that RBM47 exerts oncogenic activity by promoting M2 macrophage polarization and immune evasion. Furthermore, aberrant RBM47 expression has been implicated in postoperative cognitive dysfunction (POCD), inflammatory bowel disease (IBD), and antiviral innate immune regulation in preclinical models. This review summarizes the molecular characteristics and pathological mechanisms of RBM47, discusses the preclinical rationale for its potential utility as a biomarker and therapeutic node, and critically analyzes current research limitations, conflicting evidence, and translational bottlenecks. All biomarker and therapeutic applications discussed remain at the preclinical or retrospective-correlative stage; no RBM47-targeted intervention has entered clinical trials.
Shihua Huang, Qingsong Wang, Junhong Shen et al.· Frontiers in Immunology· 0 citations
CELF4 (CUGBP Elav-like family member 4), encoded by the human chromosome 18q12.2 locus, is an RNA-binding protein that recognizes UG-rich sequences within the 3′untranslated region (3′UTR) of target mRNAs to regulate splicing, stability, and local translation at the post-transcriptional level. Under physiological conditions, CELF4 exerts translational repression during synaptic development in the central nervous system (CNS), maintains excitatory homeostasis, and sets peripheral sensory thresholds; in cardiac fibroblasts, it is expressed at low levels and restricts baseline TGF-β signaling. In pathological states, CELF4 exhibits context-dependent bidirectional modulation: in autism spectrum disorder (ASD), major depressive disorder (MDD), epilepsy, chronic pain, and endometrial cancer, its downregulation or epigenetic silencing causes translational derepression of target mRNAs; in cardiac fibrosis, TGF-β1-induced upregulation suppresses FMO2 translation and activates the Smad2/3 pathway. Additionally, pleiotropic genetic loci near CELF4 have been linked to gut-brain axis comorbidities and obesity-hypertension syndromes. Clinically, CELF4 promoter methylation testing has entered validation trials for non-invasive endometrial cancer screening, and its haploinsufficiency has been incorporated into the genetic diagnosis of 18q12.2 microdeletion syndrome; pharmacological and gene-replacement strategies targeting CELF4 remain at the preclinical proof-of-concept stage. Here, we review the molecular regulatory networks of CELF4 and its mechanisms across multisystem diseases, discuss the current status and limitations of clinical translation, and may guide future research on diagnostic biomarkers and therapeutic strategies targeting this protein.
Qingsong Wang, Wenlong Yue, D. Lin et al.· Frontiers in Molecular Biosc...· 0 citations