Non-coding RNA Research最新文献

{"title":"The emerging regulatory roles of non-coding RNA in Ventilator-induced Lung Injury","authors":"Qianqi Xiong ,&nbsp;Ziyang Zhang ,&nbsp;Yiping Bai ,&nbsp;Li Liu ,&nbsp;Yue Zhang ,&nbsp;Jing Jia ,&nbsp;Yingying Zhang","doi":"10.1016/j.ncrna.2026.01.001","DOIUrl":"10.1016/j.ncrna.2026.01.001","url":null,"abstract":"<div><div>Ventilator-induced lung injury (VILI) is characterized by pathological features such as infiltration of inflammatory cells, increased alveolar permeability, and changes in lung compliance. The underlying mechanisms responsible for these manifestations during mechanical ventilation remain unclear. Low tidal volume ventilation and positive end-expiratory pressure (PEEP) can mitigate pulmonary edema and improve lung compliance. However, these strategies do not fully prevent VILI, and mortality remains high. Non-coding RNAs (ncRNAs) are involved in mechanotransduction processes during ventilation by modulating cellular functions through the activation of inflammatory signaling pathways, such as Toll-like receptor (TLR), Janus kinase/signal transducer and activator of transcription (JAK-STAT), and nuclear factor kappa-B (NF-κB). These pathways contribute to the development of VILI and possess notable diagnostic, differential diagnostic, and therapeutic potential. This review offers a comprehensive evaluation of current research on microRNAs and long non-coding RNAs in relevant models of VILI.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"18 ","pages":"Pages 77-86"},"PeriodicalIF":4.7,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146039439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circular RNA MALAT1 as a potential target for antimetastatic therapy","authors":"Janusz Matuszyk","doi":"10.1016/j.ncrna.2025.11.004","DOIUrl":"10.1016/j.ncrna.2025.11.004","url":null,"abstract":"<div><div>Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT1) is a long non-coding RNA (lncRNA) located in the nucleus that is involved in the regulation of gene expression and alternative splicing of gene transcription products. MALAT1 has also been implicated in processes leading to metastasis in various types of cancer. On the other hand, during the epithelial-to-mesenchymal transition (EMT) process of cancer cells, which allows the invasion and migration of cancer cells outside the primary tumor, increases in the levels of the Quaking RNA-binding protein (QKI) were found, which also led to the formation of circular RNA molecules (circRNA), including <em>MALAT1</em>-derived circRNAs. It was also found that at least some <em>MALAT1</em>-derived circRNAs could support processes leading to the spread of cancer cells outside the primary tumor. Due to the unique back-splicing junction in a given circRNA, it is possible to therapeutically target specific circRNA molecules in cancer cells while protecting linear RNAs in normal cells. Without questioning the aberrant involvement of lncRNA MALAT1 in promoting cancer cell migration and invasion, it appears that <em>MALAT1</em>-derived circRNAs, especially the circRNA known as circ-MALAT1 or circ2082 (hsa_circ_0002082), among other circRNAs, may be considered for further study as potential targets for anti-metastatic therapy.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"17 ","pages":"Pages 12-20"},"PeriodicalIF":4.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145692671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The crosstalk network of non-coding RNAs: Emerging opportunities for the clinical application of osteoporosis","authors":"Chunlu Yan ,&nbsp;Qiao Wan ,&nbsp;Zeling Fang ,&nbsp;Chuangwei Sui ,&nbsp;Xiaolong Xiao ,&nbsp;Fan Yang ,&nbsp;Baoshan Di ,&nbsp;Yajun Li ,&nbsp;Juan Yu ,&nbsp;Yana Zhao ,&nbsp;Guoliang Liu ,&nbsp;Yibo Zhou ,&nbsp;Wei Li ,&nbsp;Fangyu An","doi":"10.1016/j.ncrna.2025.11.008","DOIUrl":"10.1016/j.ncrna.2025.11.008","url":null,"abstract":"<div><div>Current methods for testing bone density lack the capability to detect patients with early bone loss, and existing osteoporosis therapies have limitations in their efficacy and safety. Therefore, the development of more precise and convenient diagnostic technologies and novel treatments is of paramount importance. Extracellular vesicle (EV)-mediated non-coding RNA (ncRNA) interaction networks enable both the detection of early bone loss and targeted therapy for enhanced treatment outcomes. In this review, we highlight the utility of EVs for carrying various ncRNAs (e.g., miRNAs, lncRNAs, and circRNAs) and thereby forming a complex regulatory network amongst bone-related cells such as osteoblasts and osteoclasts. The mechanisms through which EVs regulate bone cells and their potential for clinical translation are described in detail. Although the EV-mediated ncRNA network holds great promise for the precise diagnosis and targeted treatment of osteoporosis, rigorous large-scale studies are still required to address challenges related to its specificity and clinical application.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"17 ","pages":"Pages 90-111"},"PeriodicalIF":4.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145797814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The regulatory role of circGDI2 in hepatocellular carcinoma proliferation and glycolysis with the involvement of m6A modification","authors":"Shiyi Chen ,&nbsp;Hongxiang Xia ,&nbsp;Shuwei Chen","doi":"10.1016/j.ncrna.2025.11.006","DOIUrl":"10.1016/j.ncrna.2025.11.006","url":null,"abstract":"<div><h3>Background</h3><div>Hepatocellular carcinoma (HCC) is a highly aggressive malignancy, and metabolic reprogramming, particularly glycolysis, plays a crucial role in its progression. Circular RNAs (circRNAs) and N6-methyladenosine (m⁶A) modifications have emerged as key regulators in HCC, but the role of circGDI2 and its underlying mechanisms remain unclear.</div></div><div><h3>Objective</h3><div>This study aimed to investigate the functional role and mechanism of circGDI2 in HCC proliferation and glycolysis.</div></div><div><h3>Methods</h3><div>The expression of circGDI2 was detected by RT-qPCR. RNase R treatment was used to verify the stability of circGDI2. Functional assays, including CCK-8, glycolysis analysis (glucose consumption, lactate production), and xenograft model, were performed to assess proliferation and glycolysis. Bioinformatics prediction, MeRIP, and luciferase reporter assays were used to explore the interaction between circGDI2, IGF2BP2, and PKM2.</div></div><div><h3>Results</h3><div>CircGDI2 was highly expressed in HCC tissues and cells, and exhibited cytoplasm localization. Silencing circGDI2 inhibited Li-7 and Huh-7 cell proliferation and glycolysis, downregulated PKM2, and suppressed tumor growth. Mechanistically, circGDI2 regulated PKM2 through the m⁶A “reader” IGF2BP2, and its overexpression partially rescued the inhibitory effects of circGDI2 knockdown. Furthermore, FTO-mediated m⁶A modification enhanced circGDI2 stability and expression. Silencing FTO inhibited HCC cell proliferation, glycolysis, and tumor growth, and decreased the levels of circGDI2, IGF2BP2, and PKM2.</div></div><div><h3>Conclusions</h3><div>FTO-mediated m⁶A modification of circGDI2 promotes HCC proliferation and glycolysis via the IGF2BP2/PKM2 axis, suggesting circGDI2 as a potential therapeutic target for HCC.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"17 ","pages":"Pages 21-31"},"PeriodicalIF":4.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145692670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of cervical cell image segmentation technology based on deep learning and non-coding RNAs","authors":"Cheng Cheng ,&nbsp;Yi Yang ,&nbsp;Youshan Qu","doi":"10.1016/j.ncrna.2025.09.009","DOIUrl":"10.1016/j.ncrna.2025.09.009","url":null,"abstract":"<div><h3>Background</h3><div>Cervical cancer remains a significant health concern worldwide, necessitating effective diagnostic methods such as cervical cell image segmentation. This review outlines the challenges and importance of accurately segmenting cervical cell images in medical diagnostics.</div></div><div><h3>Objective</h3><div>This study explores the application of deep learning techniques in cervical cell image segmentation, focusing on convolutional neural networks (CNNs), fully convolutional networks, non-coding RNAs and U-Net models. It aims to compare their characteristics, strengths, and weaknesses in enhancing segmentation precision.</div></div><div><h3>Methods</h3><div>The article surveys recent advancements in deep learning-based cervical cell image segmentation, drawing insights from English literature. It highlights how CNN architectures excel in feature extraction and precise image segmentation, particularly in the context of cervical cells.</div></div><div><h3>Results</h3><div>Deep learning methodologies, particularly CNN-based models, have significantly improved the accuracy and efficiency of cervical cell image segmentation. Researchers have increasingly adopted these techniques to refine diagnostic capabilities.</div></div><div><h3>Conclusion</h3><div>The evolving landscape of cervical cell image segmentation, propelled by deep learning advancements, promises enhanced precision and efficiency in clinical diagnostics and treatment support. Future research should continue exploring these technologies to further improve medical outcomes.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"17 ","pages":"Pages 54-58"},"PeriodicalIF":4.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145749760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hsa_circ_0101645 contributes to excessive autophagy and apoptosis in intervertebral disc degeneration by acting as a miR-1304-5p sponge modulating BNIP3 expression","authors":"Jianhai Luo ,&nbsp;Tong Yu ,&nbsp;Pengcheng Hu ,&nbsp;Jie Liu","doi":"10.1016/j.ncrna.2025.11.007","DOIUrl":"10.1016/j.ncrna.2025.11.007","url":null,"abstract":"<div><h3>Background</h3><div>Intervertebral disc (IVD) degeneration (IVDD) is the pathological foundation and principal cause for degenerative spine related diseases. Currently, its molecular pathogenesis and reliable biomarkers remain poorly understood. This study intends to elucidate the potential molecular mechanisms of circular RNAs (circRNAs) in IVDD, and to identify novel targeted therapeutic strategies.</div></div><div><h3>Methods</h3><div>Differentially expressed circRNAs (DE-circRNAs) were obtained by a secondary analysis of the IVDD-related dataset GSE67566, followed by enrichment analysis of their host genes. Both <em>in vitro</em> mechanical loading-induced and <em>in vivo</em> tail suspension-induced models were applied to validate the functions of hsa_circ_0101645, miRNA-1304-05p, and BCL2 Interacting Protein 3 (BNIP3) in IVDD. The competing endogenous RNA (ceRNA) mechanism involving hsa_circ_0101645/miR-1304-5p/BNIP3 was authenticated using dual luciferase reporter genes, Argonaute2-RNA binding protein immunoprecipitation, and RNA-RNA pull down.</div></div><div><h3>Results</h3><div>In the bioinformatics, there were 354 significantly down-regulated and 282 up-regulated DE-circRNAs in IVDD. The host genes of these circRNAs were mainly enriched in cell morphogenesis, autophagy, and apoptosis. In clinical samples, hsa_circ_0101645 in DE-circRNAs was markedly overexpressed in endplate chondrocytes (EPC) derived from IVDD patients and was predominantly localized in the cytoplasm. <em>In vitro</em>, overexpression of hsa_circ_0101645 and BNIP3, or knockdown of miR-1304-5p, dramatically diminished EPC viability and enlarged apoptosis and autophagic flux. <em>In vivo</em>, sa_circ_0101645 knockdown alleviated structural collapse and tissue lesions in the cartilage endplates, nucleus pulposus and annulus fibrosus of the IVD. Mechanistically, Hsa_circ_0101645 upregulated BNIP3 expression by serving as miR-1304-5p sponge.</div></div><div><h3>Conclusions</h3><div>Hsa_circ_0101645 service as ceRNA that facilitates IVDD process by mediating proliferation, apoptosis, and excessive autophagy of CEP via the miR-1304-5p/BNIP3 axis. These findings suggest that hsa_circ_0101645 represents a promising molecular target for IVDD therapy.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"17 ","pages":"Pages 76-89"},"PeriodicalIF":4.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145797815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic H3K4me3 activation of miR-155-5p promotes intervertebral disc degeneration via autophagy and ageing in nucleus pulposus cells","authors":"Ximeng Wang ,&nbsp;Hanqiu Sun ,&nbsp;Wenbiao Xiao ,&nbsp;Yuxuan Zhang ,&nbsp;Xiao Lu ,&nbsp;Zhaoyang Gong ,&nbsp;Dachuan Li ,&nbsp;Siyang Liu ,&nbsp;Xinlei Xia ,&nbsp;Hongli Wang ,&nbsp;Minghao Shao ,&nbsp;Guangyu Xu ,&nbsp;Xiaosheng Ma","doi":"10.1016/j.ncrna.2025.12.001","DOIUrl":"10.1016/j.ncrna.2025.12.001","url":null,"abstract":"<div><div>Nucleus pulposus (NP) cell ageing and impaired autophagy - lysosome biogenesis (ALB) are key drivers of intervertebral disc degeneration (IVDD). The upstream epigenetic regulation of transcription factor EB (TFEB), a major ALB regulator, remains elusive. Our study identifies a H3K4me3-associated miRNA pathway that modulates TFEB activity and IVDD progression. Using <em>in vivo</em> and <em>in vitro</em> models, we found that methyltransferase MLL3 knockdown reduces H3K4me3 methylation at the miR-155-5p promoter, suppressing miR-155-5p transcription. MiR-155-5p directly targets FBXO22, indirectly repressing TFEB transcription and exacerbating NP cells ageing and IVDD. Notably, experiments confirmed MLL3 binds specifically to the miR-155-5p promoter, with no interaction detected at the TFEB or FBXO22 promoters. Our data establish a linear H3K4me3/miR-155-5p/FBXO22/TFEB axis in IVDD pathogenesis. We reveal a novel epigenetic crosstalk where H3K4me3 methylation mediates miRNA-driven TFEB regulation, independent of canonical mTOR signaling. These findings enhance understanding of epigenetic mechanisms in autophagy and ageing control and highlight MLL3 and miR-155-5p as potential IVDD therapeutic targets.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"17 ","pages":"Pages 112-127"},"PeriodicalIF":4.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145840625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to < ‘Characterization of small nucleolar RNA retaining transcripts in human normal and cancer cells’> <[Non-coding RNA Research vol. 13 (2025) 153–161]>","authors":"Rambaldelli G. ,&nbsp;Asghar S. ,&nbsp;Venturi G. ,&nbsp;Zacchini F. ,&nbsp;Serra M. ,&nbsp;Giovannini C. ,&nbsp;Gramantieri L. ,&nbsp;Bernini M. ,&nbsp;Inga A. ,&nbsp;Dassi E. ,&nbsp;Montanaro L.","doi":"10.1016/j.ncrna.2026.01.002","DOIUrl":"10.1016/j.ncrna.2026.01.002","url":null,"abstract":"","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"17 ","pages":"Page 160"},"PeriodicalIF":4.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146038054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LncRNA ZFAS1 in hepatocellular carcinoma: A systematic review of molecular mechanisms and clinical translation","authors":"Peng Zhu ,&nbsp;Hui-ying Liu","doi":"10.1016/j.ncrna.2025.11.003","DOIUrl":"10.1016/j.ncrna.2025.11.003","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality globally, with its high recurrence rate and therapeutic resistance underscoring the urgent need for breakthrough molecular targets. The long non-coding RNA ZFAS1 has emerged as a critical regulatory hub in HCC pathogenesis through its multidimensional mechanisms. Clinical investigations reveal significant ZFAS1 overexpression in HCC tissues, which is strongly associated with microvascular invasion, lymph node metastasis, and unfavorable clinical outcomes. Meta-analytical data further corroborate its independent prognostic value in survival prediction.</div><div>Mechanistically, ZFAS1 functions as a competitive endogenous RNA (ceRNA) that sequesters tumor-suppressive miRNAs including miR-150 and miR-193a-3p, thereby de-repressing downstream oncogenic targets such as ZEB1/MMP14 and RALY/HGF/c-Met. This molecular interplay drives epithelial-mesenchymal transition (EMT) and metastatic progression, while ZFAS1-encoded micropeptides concurrently inhibit ferroptosis through mitochondrial ROS modulation and the miR-150/AIFM2 axis, thereby synergistically enhancing tumor proliferation and apoptotic resistance. Within the tumor microenvironment (TME), exosome-derived ZFAS1 remodels intercellular communication networks, promoting angiogenesis via STAT3/VEGFA signaling, though its immunometabolic regulatory mechanisms warrant further elucidation. Clinically, plasma ZFAS1 demonstrates enhanced diagnostic utility when combined with alpha-fetoprotein (AUC = 0.891), while therapeutic targeting of ZFAS1-mediated PI3K-AKT and PERK/ATF4 pathways shows promise in overcoming sorafenib/donafenib resistance. Current translational challenges include ZFAS1 isoform heterogeneity, suboptimal liquid biopsy sensitivity, and dynamic TME interactions.</div><div>Future directions should employ multi-omics integration (spatial transcriptomics/single-cell sequencing) coupled with AI-driven network modeling to systematically decode ZFAS1's regulatory architecture, ultimately enabling precision theranostic strategies for HCC management.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"17 ","pages":"Pages 44-53"},"PeriodicalIF":4.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145692651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SNHG5 enhances colorectal cancer metastasis through RNA–protein interaction with GNB2 and activation of canonical Wnt signaling","authors":"Xinyi Chen ,&nbsp;Mu Yang ,&nbsp;Xiaoxiao Luo,&nbsp;Xianglin Yuan","doi":"10.1016/j.ncrna.2025.12.002","DOIUrl":"10.1016/j.ncrna.2025.12.002","url":null,"abstract":"<div><h3>Background and purpose</h3><div>Colorectal cancer (CRC) is one of the most prevalent and lethal malignancies worldwide, with distant metastasis—particularly to the liver—representing the primary cause of poor prognosis. Long non-coding RNAs (lncRNAs) have emerged as critical regulators of CRC progression, yet the mechanisms by which they modulate G protein signaling during hepatic metastasis remain unclear. This study aimed to determine the role of the lncRNA SNHG5 in CRC liver metastasis and to explore whether G protein–related mechanisms are involved in this process.</div></div><div><h3>Methods</h3><div>We established murine MC38 CRC sublines with distinct metastatic capacities (F0 and F3) and performed RNA sequencing to identify key lncRNAs. Biotin-labeled RNA pull-down coupled with mass spectrometry was used to identify SNHG5-interacting proteins. The SNHG5–GNB2 interaction was validated using RIP, RNA-FISH, and Western blot analyses. Functional rescue assays, in vivo liver metastasis models, and Wnt pathway activity measurements were conducted to delineate downstream effects. Public transcriptomic datasets from GEO and TCGA were used to assess the expression patterns and prognostic relevance of SNHG5 and GNB2 in CRC and metastatic lesions.</div></div><div><h3>Results</h3><div>SNHG5 was significantly upregulated in the highly metastatic F3 subline and predominantly localized in the cytoplasm. Pull-down and proteomic analysis identified GNB2, a classical G protein β-subunit, as a direct binding partner of SNHG5. Functionally, SNHG5 promoted cell proliferation, migration, epithelial–mesenchymal transition (EMT), and suppressed apoptosis, while GNB2 overexpression partially rescued the tumor-suppressive phenotypes induced by SNHG5 silencing. Mechanistically, the SNHG5–GNB2 axis enhanced Wnt/β-catenin signaling via increased p-GSK3β and β-catenin levels, thereby driving EMT. Transcriptomic analyses further revealed that GNB2 is upregulated in CRC and liver metastases and is associated with poor prognosis. Multi-omics data suggested additional roles for this axis in immune evasion, metabolic reprogramming, and remodeling of the metastatic microenvironment.</div></div><div><h3>Conclusion</h3><div>This study provides the first evidence that SNHG5 promotes CRC liver metastasis through direct interaction with GNB2 and subsequent activation of the Wnt/β-catenin pathway. The SNHG5–GNB2 axis orchestrates a multilayered regulatory network that integrates EMT induction, immune suppression, and metabolic adaptation, highlighting its potential as a mechanistic driver and therapeutic target in metastatic CRC.</div></div>","PeriodicalId":37653,"journal":{"name":"Non-coding RNA Research","volume":"17 ","pages":"Pages 128-149"},"PeriodicalIF":4.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145884388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}