The molecular characteristics and pathological mechanisms of RBM47 are summarized, the preclinical rationale for its potential utility as a biomarker and therapeutic node is discussed, and current research limitations, conflicting evidence, and translational bottlenecks are critically analyzed.
Abstract
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.
BACKGROUND
Cervical cancer (CC) is a prevalent malignancy in women. RNA-binding motif single-stranded interacting protein 3 (RBMS3) acts as a tumor suppressor in many cancer types, but its role and underlying regulatory mechanisms in CC remain unclear.
METHODS
The expression levels of RBMS3 and heat shock protein family A member 6 (HSPA6) were evaluated in clinical CC tissues. Gain- and loss-of-function assays, transcriptome sequencing, and rescue experiments were performed in CC cell lines and nude mouse xenograft models.
RESULTS
RBMS3 expression was notably lower in CC tissues (n = 306) than in normal cervical tissues (n = 22), with reduced levels linked to shorter overall patient survival (p < 0.05). Overexpression of RBMS3 reduced cell proliferation, migration, and invasion in vitro, as well as tumor growth in vivo (p < 0.001). HSPA6 was identified as a key target of RBMS3 and was also downregulated in CC tissues. RBMS3 potentially binds to HSPA6 mRNA and enhances its stability. Knockdown of HSPA6 reversed the tumor-suppressive effects of RBMS3 (p < 0.001).
CONCLUSIONS
RBMS3 inhibits CC progression by stabilizing HSPA6 mRNA. The RBMS3-HSPA6 axis may represent a prognostic biomarker and therapeutic target in CC.
Huaping Huang, Ping Li, Lixia Zhu et al.· Frontiers in Bioscience· 0 citations
Simple Summary Tumor metastasis is one of the key causes of cancer-related deaths, including lung cancer. However, the mechanism controlling the expression of metastasis-related genes has still not been completely clarified, especially the post-transcriptional regulation mechanism mediated by RNA-binding proteins (RBPs) in human lung cancer cells. Here, we revealed that the RBPs MCPIP3 (monocyte chemotactic protein-induced protein 3) and IGF2BP3 (insulin-like growth factor 2 mRNA-binding protein 3) negatively and positively regulate lung cancer cell metastasis, respectively, by antagonistically regulating METAP2 (methionine aminopeptidase 2) mRNA stability and expression through targeting the same stem–loop structure. These findings provide new insights into the yin–yang effects of RBPs in mediating metastasis-related gene expression in human lung cancer cells and may provide potential molecular targets for lung cancer treatment.
Shaoyu Song, Hong-wei Li, Ailing Li et al.· Cancers· 0 citations
: Background: Circular RNAs have emerged as important regulators of non-small cell lung cancer progression through competing endogenous RNA networks, but the specific role and mechanism of CircATRNL1 in NSCLC remain unclear. This study investigates the mechanistic role of CircATRNL1 in the malignant progression of non-small cell lung cancer (NSCLC). Methods: Gene expression levels in NSCLC cell lines were quantified using reverse transcription quantitative PCR (RT-qPCR). Functional assays, including Western blot analysis of epithelial– mesenchymal transition (EMT)-related proteins, wound-healing assays, and Transwell migration and invasion assays, were performed to assess the effects of CircATRNL1 on cellular motility and invasive potential. Potential RNA–RNA interactions were predicted using the ENCORI and CircBank databases, followed by luciferase reporter assays to validate these interactions experimentally. To determine whether the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway mediated the biological effects of insulin-like growth factor-binding protein 3 (IGFBP3), rescue experiments were performed using the PI3K inhibitor LY294002. Results: CircATRNL1 was significantly upregulated in NSCLC cell lines and showed typical circular RNA characteristics, including RNase R resistance and enhanced transcript stability (*** p < 0.001). CircATRNL1 knockdown inhibited NSCLC cell migration and invasion, whereas CircATRNL1 overexpression exerted the opposite effects. Mechanistically, CircATRNL1 functioned as a sponge for miR-103a-3p and relieved miR-103a-3p mediated repression of IGFBP3, as validated by luciferase reporter and rescue assays (** p < 0.01). IGFBP3 further activated PI3K/AKT signaling by increasing p-PI3K/PI3K and p-AKT/AKT ratios, while LY294002 attenuated IGFBP3-induced migration and invasion. Conclusions: CircATRNL1 promotes NSCLC cell migration and invasion by acting as a ceRNA for miR-103a-3p, thereby regulating IGFBP3 and activating PI3K/AKT signalling. These findings highlight the CircATRNL1/miR-103a-3p/IGFBP3/PI3K-AKT axis as a potential regulatory mechanism contributing to in vitro migration and invasion in NSCLC.
Jiawei Liu, Tao Huang, Qi You et al.· Biocell (Mendoza)· 0 citations
ABSTRACT RNA‐binding proteins (RBPs) are central regulators of post‑transcriptional gene expression, controlling RNA stability, localization, translation, and alternative splicing. Their functions arise not only from intrinsic RNA‐binding domains but also from dynamic interactions with noncoding RNAs, metabolites, cofactors, and other RBPs. Here, we summarize the structural diversity and core biological activities of canonical and noncanonical RBPs, and delineate how competitive and cooperative regulatory networks dictate RBP function in disease, with an emphasis on cancer. Competitive mechanisms, including lncRNA‐mediated sequestration, antagonistic crosstalk between miRNAs and RBPs, and competition among RBPs for shared substrates, can redirect RNA fate. In contrast, cooperative mechanisms assemble multimolecular ribonucleoprotein complexes that reinforce oncogenic or tumor‐suppressive programs. Dysregulation of these networks promotes proliferation, metastasis, immune evasion, and therapy resistance. We also review emerging therapeutic strategies that target RBP‐centered regulatory circuits, including antisense oligonucleotides, small molecules, protein degraders, and natural products, and we evaluate representative preclinical studies and clinical trials. By integrating mechanistic principles with translational evidence, this review provides a network‐based framework for exploiting RBPs as therapeutic vulnerabilities and for advancing next‐generation precision oncology.
Ling Li, Xiu-Li Yan, Qing Ji et al.· MedComm· 0 citations
Butyrophilin-like 9 (BTNL9), a member of the immunoglobulin superfamily containing a bZIP-like domain, has a poorly defined role in cancer. Here, we identify BTNL9 as a non-canonical transcriptional regulator and investigate its function in non-small cell lung cancer (NSCLC). Coiled-coil prediction, native PAGE, and co-immunoprecipitation demonstrated BTNL9 homodimerization via its bZIP-like region, while subcellular fractionation and immunofluorescence confirmed its presence in both the nucleus and cytoplasm. Chromatin immunoprecipitation sequencing (ChIP-seq) analysis identified 9709 BTNL9-associated genomic regions, including sites proximal to transcription start sites, with enrichment of a cytosine-rich motif. Whether chromatin association reflects direct DNA binding or indirect co-regulatory interaction remains to be experimentally confirmed. Integrated transcriptomic and protein analyses revealed that BTNL9 overexpression represses genes involved in cell cycle progression and DNA replication while activating a subset of p53-associated pathways. Consistently, functional assays showed that increased BTNL9 expression induces cell cycle arrest, suppresses proliferation and clonogenicity, and inhibits tumor growth in xenograft models. In addition, cytotoxicity assays demonstrated enhanced sensitivity to bortezomib, with context-dependent effects on etoposide response. Analysis of public clinical datasets further showed that low BTNL9 expression is associated with advanced tumor stage, reduced remission rates, and poorer survival outcomes in NSCLC. These findings identify BTNL9 as a non-canonical tumor-suppressive transcriptional regulator with potential biomarker relevance in NSCLC.
W. Ng, P. Yadollahi, Hwa Jin Cho et al.· International Journal of Mol...· 0 citations
Non-small cell lung cancer (NSCLC) imposes a substantial global disease burden. Kelch repeat and BTB domain-containing protein 10 (KBTBD10) constitutes a subunit of E3 ubiquitin ligase complexes and participates in the ubiquitin-proteasome system. Mounting evidence has demonstrated that long non-coding RNAs (lncRNAs) exert critical regulatory effects in NSCLC progression. Herein, we systematically characterized the biological functions and underlying mechanisms of lncRNA LINC01585 and KBTBD10 in NSCLC. We interrogated gene expression patterns using TIMER 2.0 and Kaplan-Meier survival analysis, and further validated KBTBD10 protein expression in clinical NSCLC specimens via immunohistochemistry. Mechanistically, KBTBD10 exerted tumor-suppressive effects in NSCLC by facilitating the ubiquitin-mediated degradation of fused in sarcoma (FUS), whereas FUS upregulated LINC01585 transcription. Clinically, reduced KBTBD10 expression correlated with unfavorable patient survival outcomes. Functionally, LINC01585 promoted the acetylation of cytoplasmic poly(A)-binding protein 1 (PABPC1) and drove oncogenic phenotypes in NSCLC through activation of the signal transducer and activator of transcription 3 (STAT3) signaling cascade. In vitro cellular assays further revealed that LINC01585 boosted interleukin-6 (IL-6) secretion, which establishes a self-amplifying LINC01585/STAT3/IL-6 positive feedback circuit and underscores the vital contribution of the tumor immune microenvironment to NSCLC pathogenesis. Collectively, our study delineates a multilayered regulatory signaling axis linking the immunogenomic microenvironment to NSCLC progression. These results provide mechanistic insights and translational implications for developing immunotherapeutic strategies targeting KBTBD10, and LINC 01585 in NSCLC treatment.
Xizi Jiang, J. Guan, Kexin Liang et al.· International Immunopharmaco...· 0 citations