Non-coding RNA Research最新文献_第9页

Tongue squamous cell carcinoma-derived exosomes miR-21-5p affect tumor progression via promoting M2 macrophage polarization 舌鳞癌源性外泌体miR-21-5p通过促进M2巨噬细胞极化影响肿瘤进展

IF 5.9 3区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Non-coding RNA Research

Pub Date : 2025-08-01 Epub Date: 2025-05-15 DOI: 10.1016/j.ncrna.2025.05.006

Zixian Xu , Xin Fang , Shan Wang , Jiabei Mu , Qixian Gai , Yantong Chen , Zheyi Sun , Jiemei Zhai

Exosome-mediated intercellular communication plays a key role in shaping the tumor microenvironment and promoting tumor progression. Recent studies have demonstrated that tumor exosomal miRNAs significantly contribute to the polarization of tumor-associated macrophages (TAMs). However, the molecular mechanisms underlying miRNA-mediated regulation of macrophage polarization by exosomes derived from tongue squamous cell carcinoma (TSCC) remain incompletely elucidated. In this study, small RNA sequencing analysis of exosomal miRNAs revealed miR-21-5p was highly expressed in TSCC-derived exosomes. Further investigation demonstrated a significant association between exosomal miR-21-5p and M2 polarization of tumor-associated macrophages (TAMs). Functionally, TSCC-derived exosomes promoted the polarization of M0 macrophages towards the M2 phenotype. Mechanistically, exosomal miR-21-5p enhanced M2 polarization of TAMs by inhibiting phosphorylation of ERK1/2. Additionally, we performed single-sample gene set enrichment analysis (ssGSEA), constructed a multivariate Cox regression model, and performed survival analysis using paired RNA transcriptome and clinical data from TSCC patients. Our results revealed a significant enrichment of M2 macrophages in the tumor microenvironment (TME) of TSCC compared to adjacent normal tissue. Furthermore, we confirmed that M2 macrophages infiltration is associated with poor prognosis in TSCC patients. In summary, our study demonstrates that TSCC-derived exosomal miR-21-5p plays an critical role in M2 macrophage polarization, and M2 macrophages infiltration contributes to the progression of TSCC. Therefore, these findings suggest that therapeutic targeting of miR-21-5p may represent a novel strategy for TSCC treatment by selectively modulating the M2 polarization of TAMs.

外泌体介导的细胞间通讯在塑造肿瘤微环境和促进肿瘤进展中起着关键作用。最近的研究表明，肿瘤外泌体mirna显著促进肿瘤相关巨噬细胞（tam）的极化。然而，来自舌鳞状细胞癌（TSCC）的外泌体通过mirna介导巨噬细胞极化调节的分子机制尚未完全阐明。在这项研究中，外泌体miRNAs的小RNA测序分析显示，miR-21-5p在tscc衍生的外泌体中高度表达。进一步的研究表明，外泌体miR-21-5p与肿瘤相关巨噬细胞（tam）的M2极化之间存在显著关联。功能上，tscc衍生的外泌体促进M0巨噬细胞向M2表型极化。机制上，外泌体miR-21-5p通过抑制ERK1/2的磷酸化来增强tam的M2极化。此外，我们进行了单样本基因集富集分析（ssGSEA），构建了多变量Cox回归模型，并使用配对RNA转录组和TSCC患者的临床数据进行了生存分析。我们的研究结果显示，与邻近正常组织相比，TSCC肿瘤微环境（TME）中M2巨噬细胞显著富集。此外，我们证实M2巨噬细胞浸润与TSCC患者预后不良有关。综上所述，我们的研究表明，TSCC来源的外泌体miR-21-5p在M2巨噬细胞极化中起关键作用，M2巨噬细胞浸润有助于TSCC的进展。因此，这些发现表明，靶向治疗miR-21-5p可能是一种通过选择性调节tam的M2极化来治疗TSCC的新策略。

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引用次数: 0

The role of non-coding RNA regulates stem cell programmed death in disease therapy 非编码RNA在疾病治疗中调控干细胞程序性死亡的作用

IF 5.9 3区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Non-coding RNA Research

Pub Date : 2025-08-01 Epub Date: 2025-04-23 DOI: 10.1016/j.ncrna.2025.04.005

Ziling Liao , Weidong Liu , Lei Wang , Wen Xie , Chaoyan Yao , Qianping Huang , Xingjun Jiang , Caiping Ren

Programmed cell death (PCD), an essential and inevitable phenomenon, is integral to organismal development. It not only maintains cellular homeostasis but also prevents aberrant cell proliferation, thereby protecting normal growth and development from detrimental factors. And it is governed by a highly complex and sophisticated regulatory network in which non-coding RNAs (ncRNAs) play pivotal roles. ncRNAs refer to RNA molecules that do not encode proteins and encompass various types, including long non-coding RNA (lncRNA), microRNA (miRNA), and circular RNA (circRNA). Herein, we investigate the specific signaling mechanisms by which ncRNAs regulate stem cells, elucidating their role in modulating PCD process through interactions with specific molecules. We further summarize the impact of above modulating role on stem cell differentiation, proliferation, cycle regulation and diverse disease development and therapy. Additionally, given the emerging trends in the therapeutic application of ncRNAs and stem cells, we explore the potential of their combined application for disease treatment.

细胞程序性死亡（PCD）是机体发育过程中不可避免的重要现象。它不仅能维持细胞的稳态，还能防止细胞的异常增殖，从而保护正常的生长发育免受有害因素的影响。它是由一个高度复杂和复杂的调控网络控制的，其中非编码rna （ncrna）起着关键作用。ncrna是指不编码蛋白质的RNA分子，包含多种类型，包括长链非编码RNA （lncRNA）、微RNA （miRNA）和环状RNA （circRNA）。在此，我们研究了ncRNAs调节干细胞的特定信号机制，阐明了它们通过与特定分子的相互作用在调节PCD过程中的作用。我们进一步总结了上述调节作用对干细胞分化、增殖、周期调控以及多种疾病发生和治疗的影响。此外，鉴于ncrna和干细胞治疗应用的新趋势，我们探索它们联合应用于疾病治疗的潜力。

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引用次数: 0

Uremic toxins levels are associated with miR-223 in chronic kidney disease-associated anemia 慢性肾病相关性贫血患者尿毒症毒素水平与miR-223相关

IF 5.9 3区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Non-coding RNA Research

Pub Date : 2025-08-01 Epub Date: 2025-05-02 DOI: 10.1016/j.ncrna.2025.04.009

Emma Brisot , Pierre-Marie Leprêtre , Eya Hamza , Ophélie Fourdinier , Benjamin Brigant , Hakim Ouled-Haddou , Gabriel Choukroun , Ziad A. Massy , Francis Verbeke , Valérie Metzinger-Le Meuth , Griet Glorieux , Laurent Metzinger

Chronic kidney disease (CKD) poses a significant threat, with increased rates of cardiovascular and all-cause mortality. Anemia, common in CKD, is associated with accumulation of uremic toxins in the bloodstream. We previously demonstrated that the uremic toxin indoxyl sulfate (IS) impacts the regulation of erythropoiesis in cellular and preclinical CKD models. Here, the role of non-coding RNAs in this toxic effect was evaluated. The effect of IS on microRNA expression was measured in human erythropoietic cell line UT7/EPO, using nanostring. We found a significant increase of miR-223 in cells treated with IS. This finding was further validated in human primary CD34⁺ cells, a more physiological model for human erythropoiesis. Finally, serum levels of miR-223 correlated with representative uremic toxins, including IS, in patients with various stages of CKD, and also with endothelial dysfunction markers, indicating a link with vascular damage. These correlations varied according to erythropoietin treatment and dialysis. These findings suggest that miR-223 may play a role in the development of anemia in CKD. Further investigation into the involvement of miR-223 in erythropoiesis is needed for a better understanding of the mechanisms underlying anemia in CKD and the potential role of uremic toxins. Ultimately, this may open up new therapeutic possibilities for the management of anemia in CKD.

慢性肾脏疾病（CKD）具有显著的威胁，心血管和全因死亡率增加。慢性肾病中常见的贫血与血液中尿毒症毒素的积累有关。我们之前证明了尿毒症毒素硫酸吲哚酚（IS）在细胞和临床前CKD模型中影响红细胞生成的调节。本研究评估了非编码rna在这种毒性作用中的作用。采用纳米链法检测IS对人红细胞UT7/EPO细胞microRNA表达的影响。我们发现在IS处理的细胞中miR-223显著增加。这一发现在人原代CD34+细胞中得到了进一步验证，这是一种更生理的人红细胞生成模型。最后，在不同阶段CKD患者中，血清miR-223水平与代表性尿毒症毒素（包括IS）相关，也与内皮功能障碍标志物相关，表明与血管损伤有关。这些相关性根据促红细胞生成素治疗和透析而变化。这些发现提示miR-223可能在CKD中贫血的发展中发挥作用。为了更好地了解CKD中贫血的潜在机制和尿毒症毒素的潜在作用，需要进一步研究miR-223在红细胞生成中的作用。最终，这可能为慢性肾病贫血的治疗开辟新的可能性。

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引用次数: 0

Exosomes derived let-7f-5p is a potential biomarker of SLE with anti-inflammatory function 外泌体衍生的let-7f-5p是SLE具有抗炎功能的潜在生物标志物

IF 5.9 3区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Non-coding RNA Research

Pub Date : 2025-06-01 Epub Date: 2025-02-21 DOI: 10.1016/j.ncrna.2025.02.004

Yi-jing Liu , Hai-bing Miao , Shu Lin , Zhen Chen

This study found that in patients with SLE (n = 5), lethal (let)-7f-5p expression was significantly downregulated in peripheral blood mononuclear cells. Further, high-throughput RNA sequencing was used to mine the differential transcriptome expression in renal tissue exosomes of systemic lupus erythematosus (SLE)-prone mice, and bioinformatics was utilized to analyze non-coding RNAs and coding RNAs in exosomes for their possible roles in SLE. In renal tissues of MRL/lpr SLE-prone mice with exosomes and Pristane-induced SLE mice, we also demonstrated aberrant expression levels of microRNA (miRNA) let-7f-5p. Meanwhile, in the macrophage inflammation model, the expression levels of let-7f-5p were downregulated, that of guanylate binding protein (Gbp2 and Gbp7) were upregulated, and the inflammatory state of macrophages was alleviated following transfection with the let-7f-5p mimic. Co-culturing mesenchymal stem cells with a macrophage model of inflammation resulted in increased let-7f-5p expression and downregulated inflammatory factors, Gbp2 and Gbp7 expression in macrophages. Dual luciferase reporter gene assays confirmed that let-7f-5p directly binds to the 3′ UTR of Gbp7 to regulate its expression. Let-7f-5p regulation of the Gbp family is involved in SLE pathogenesis and is a biomarker associated with the inflammatory response with potential clinical applications.

本研究发现，在SLE患者（n = 5）中，外周血单个核细胞中致命性(let)-7f-5p表达显著下调。此外，利用高通量RNA测序技术挖掘系统性红斑狼疮（SLE）易感小鼠肾组织外泌体的差异转录组表达，并利用生物信息学分析外泌体中的非编码RNA和编码RNA在SLE中的可能作用。在带有外泌体的MRL/lpr SLE易感小鼠和普里斯坦诱导的SLE小鼠的肾组织中，我们也发现了microRNA (miRNA) let-7f-5p的异常表达水平。同时，在巨噬细胞炎症模型中，转染let-7f-5p模拟物后，可下调let-7f-5p的表达水平，上调鸟苷酸结合蛋白（Gbp2和Gbp7）的表达水平，减轻巨噬细胞的炎症状态。间充质干细胞与巨噬细胞炎症模型共培养导致巨噬细胞中let-7f-5p表达升高，炎症因子Gbp2和Gbp7表达下调。双荧光素酶报告基因检测证实let-7f-5p直接结合Gbp7的3 ' UTR调控其表达。Gbp家族的Let-7f-5p调控参与SLE发病机制，是与炎症反应相关的生物标志物，具有潜在的临床应用价值。

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引用次数: 0

Non-coding RNA-mediated granulosa cell dysfunction during ovarian aging: From mechanisms to potential interventions 卵巢衰老过程中非编码rna介导的颗粒细胞功能障碍：从机制到潜在的干预措施

IF 5.9 3区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Non-coding RNA Research

Pub Date : 2025-06-01 Epub Date: 2025-03-03 DOI: 10.1016/j.ncrna.2025.03.001

Li Dong , Haicui Wu , Fanghua Qi , Yuan Xu , Wen Chen , Yuqi Wang , Pingping Cai

As the earliest aging organ in the reproductive system, the ovary has both reproductive and endocrine functions, which are closely related to overall female health. The exact pathogenesis of ovarian aging (OA) remains incompletely understood, with granulosa cells (GCs) dysfunction playing a significant role in this process. Recent advancements in research and biotechnology have highlighted the importance of non-coding RNAs (ncRNAs), including micro RNAs, long non-coding RNAs, and circular RNAs, in regulating the biological functions of GCs through gene expression modulation. This paper provides a comprehensive overview of the role of ncRNAs in various cellular functions such as apoptosis, autophagy, proliferation, and steroid synthesis in GCs, and explores the underlying regulatory mechanisms. Additionally, the therapeutic potential of ncRNAs, particularly those carried by exosomes derived from mesenchymal stem cells, in delaying OA is discussed. Understanding the regulatory mechanisms of ncRNAs in GC function and the current progress in this field is crucial for identifying effective biomarkers and therapeutic targets, ultimately aiding in the early diagnosis, prognostic assessment, and individualized treatment of OA.

卵巢作为生殖系统中最早衰老的器官，兼具生殖和内分泌功能，与女性整体健康密切相关。卵巢衰老（OA）的确切发病机制尚不完全清楚，颗粒细胞（GCs）功能障碍在这一过程中起着重要作用。近年来研究和生物技术的进展突出了非编码rna （ncRNAs）的重要性，包括微rna、长链非编码rna和环状rna，它们通过基因表达调节来调节GCs的生物学功能。本文全面综述了ncRNAs在GCs中凋亡、自噬、增殖和类固醇合成等多种细胞功能中的作用，并探讨了其潜在的调控机制。此外，本文还讨论了ncrna的治疗潜力，特别是来自间充质干细胞的外泌体携带的ncrna，在延缓OA方面的作用。了解ncrna在GC功能中的调控机制以及该领域的最新进展，对于确定有效的生物标志物和治疗靶点，最终有助于OA的早期诊断、预后评估和个体化治疗至关重要。

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引用次数: 0

miR-210 overexpression increases pressure overload-induced cardiac fibrosis miR-210过表达增加压力过载引起的心脏纤维化

IF 5.9 3区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Non-coding RNA Research

Pub Date : 2025-06-01 Epub Date: 2025-01-31 DOI: 10.1016/j.ncrna.2025.01.009

G. Zaccagnini , D. Baci , S. Tastsoglou , I. Cozza , A. Madè , C. Voellenkle , M. Nicoletti , C. Ruatti , M. Longo , L. Perani , C. Gaetano , A. Esposito , F. Martelli

Aortic stenosis, a common valvular heart disease, can lead to left ventricular pressure overload, triggering pro-fibrotic responses in the heart. miR-210 is a microRNA that responds to hypoxia and ischemia and plays a role in immune regulation and in cardiac remodeling upon myocardial infarction. This study investigated the effects of miR-210 on cardiac fibrosis caused by pressure overload.

Using a mouse model with inducible miR-210 over-expression, we subjected mice to transverse aortic constriction (TAC) to induce pressure overload. Mice with miR-210 over-expression developed eccentric hypertrophy, heightened expression of hypertrophic markers (Nppa and Nppb) and increased cross sectional area of cardiomyocytes, impacting the free wall of the left ventricle. These findings suggest that miR-210 worsens cardiac dysfunction. Furthermore, miR-210 over-expression led to a more robust and sustained inflammatory response in the heart, increased interstitial and perivascular fibrosis, and activation of myofibroblasts. miR-210 also promoted angiogenesis. In vitro, cardiac fibroblasts over-expressing miR-210 showed increased adhesion, wound healing and migration capacity.

Our results demonstrate that miR-210 contributes to adverse cardiac remodeling in response to pressure overload, including eccentric hypertrophy, inflammation, and fibrosis.

主动脉瓣狭窄是一种常见的瓣膜性心脏病，可导致左心室压力过载，引发心脏促纤维化反应。miR-210是一种响应缺氧和缺血的microRNA，在心肌梗死后的免疫调节和心脏重构中发挥作用。本研究探讨了miR-210在压力过载引起的心脏纤维化中的作用。使用诱导miR-210过表达的小鼠模型，我们对小鼠进行横断主动脉收缩（TAC）以诱导压力过载。miR-210过表达的小鼠出现偏心肥厚，肥厚标志物（Nppa和Nppb）表达升高，心肌细胞横截面面积增加，影响左心室自由壁。这些发现提示miR-210加重心功能障碍。此外，miR-210过表达导致心脏中更强烈和持续的炎症反应，增加间质和血管周围纤维化，并激活肌成纤维细胞。miR-210也促进血管生成。在体外，过表达miR-210的心脏成纤维细胞显示出粘连、伤口愈合和迁移能力的增强。我们的研究结果表明，miR-210在压力过载的反应中有助于不良的心脏重塑，包括偏心肥大、炎症和纤维化。

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引用次数: 0

Suppression of endometriosis by miRNA-34a via inhibition of matrix metalloproteinase-2: An alternative pathway to impede invasion miRNA-34a通过抑制基质金属蛋白酶-2抑制子宫内膜异位症：阻止侵袭的另一途径

IF 5.9 3区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Non-coding RNA Research

Pub Date : 2025-06-01 Epub Date: 2025-02-24 DOI: 10.1016/j.ncrna.2025.02.001

Yasmin Begum , Anuradha Pandit , Devendra Shukla , Rahul Gupta , Pramathes DasMahapatra , Amit Kumar Srivastava , Snehasikta Swarnakar

Matrix metalloproteinases (MMPs) cleave proteins of extracellular matrix thus facilitating cellular invasion and cancer progression. High MMP-2 activity is frequently reported in several diseases including endometriosis and cancer. Endometriosis, though benign causing pain and infertility, rarely culminate into ovarian cancer. New diagnostic markers are needed for early diagnosis and proper therapeutic avenues since the only diagnostic method is laparoscopy to date. Emerging evidence shows the importance of MMP activity and involvement of noncoding RNA, e.g. miRNA thereon. We investigated the role of miRNA-34a in MMP-2-mediated regulation of invasion and tumorigenesis in endometriosis. Database analysis showed a decreased miRNA-34a in different gynecological malignancies. qRT-PCR with human endometriotic and control tissues revealed a significant elevation in MMP-2 activity with downregulated miR-34a in diseased individuals proving an inverse correlation between miRNA-34a and MMP-2. Luciferase assay in SK-OV-3 cells demonstrated that miRNA-34a-5p directly binds the 3′UTR of the MMP-2 promoter to reduce its transcription followed by suppression of invasion. The zymographic assay also showed a reduced MMP-2 activity upon miR-34a treatment in End1/E6E7 and SK-OV-3 cells. We also found that miRNA-34a-5p inhibits invasion, migration, colony/spheroid formation, and stemness of the cells thereby reducing in vitro tumorigenesis. Subsequently, the immunoblotting results confirmed that MMP-2, and mesenchymal markers like n-cadherin, vimentin, and slug expression were downregulated, whereas the e-cadherin was upregulated in the cells treated with miRNA-34a mimic. Our study demonstrates the direct binding of miR-34a-5p with the MMP-2 gene's 3′UTR and thus repressed its transcription as well as suppressing endometriosis progression.

基质金属蛋白酶（Matrix metalloproteinases, MMPs）可切割细胞外基质蛋白，从而促进细胞侵袭和癌症进展。高MMP-2活性经常被报道在包括子宫内膜异位症和癌症在内的几种疾病中。子宫内膜异位症虽然是良性的，会引起疼痛和不孕，但很少会发展成卵巢癌。由于迄今为止唯一的诊断方法是腹腔镜检查，因此需要新的诊断标志物来进行早期诊断和适当的治疗途径。新出现的证据表明MMP活性和非编码RNA（如miRNA）参与的重要性。我们研究了miRNA-34a在mmp -2介导的子宫内膜异位症侵袭和肿瘤发生调控中的作用。数据库分析显示，miRNA-34a在不同妇科恶性肿瘤中表达降低。对人子宫内膜异位症和对照组织的qRT-PCR显示，患病个体的MMP-2活性显著升高，miR-34a下调，证明miRNA-34a与MMP-2呈负相关。SK-OV-3细胞的荧光素酶测定表明，miRNA-34a-5p直接结合MMP-2启动子的3'UTR，减少其转录，抑制其侵袭。酶谱分析还显示，在End1/E6E7和SK-OV-3细胞中，miR-34a处理后MMP-2活性降低。我们还发现miRNA-34a-5p抑制细胞的侵袭、迁移、集落/球状体形成和干性，从而减少体外肿瘤发生。随后，免疫印迹结果证实，在miRNA-34a模拟物处理的细胞中，MMP-2和间充质标记物如n-cadherin、vimentin和slug的表达下调，而e-cadherin的表达上调。我们的研究表明miR-34a-5p与MMP-2基因的3'UTR直接结合，从而抑制其转录并抑制子宫内膜异位症的进展。

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引用次数: 0

LURAP1L-AS1 long noncoding RNA promotes breast cancer progression and associates with poor prognosis LURAP1L-AS1长链非编码RNA促进乳腺癌进展并与不良预后相关

IF 5.9 3区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Non-coding RNA Research

Pub Date : 2025-06-01 Epub Date: 2025-01-19 DOI: 10.1016/j.ncrna.2025.01.006

Radhakrishnan Vishnubalaji , Dania Awata , Nehad M. Alajez

Long noncoding RNAs (lncRNAs) are emerging as critical regulators of cancer biology, yet their roles in breast cancer, particularly in triple-negative breast cancer (TNBC), remain incompletely understood. Through a custom siRNA library screen targeting TNBC-associated lncRNAs in MDA-MB-231 and BT-549 TNBC cell models, we identified LURAP1L-AS1 as a key modulator of TNBC progression. Survival analysis of TNBC patients demonstrated a significant association between elevated LURAP1L-AS1 expression and poor clinical outcomes.

LURAP1L-AS1 knockdown significantly impaired colony formation and organoid growth of TNBC models, associated with increased apoptosis thus highlighting its role in promoting tumorigenicity. RNA sequencing of LURAP1L-AS1-depleted cells revealed dysregulation of pathways related to cell proliferation, apoptosis, migration, and RNA processing. Bioinformatics analysis predicted LURAP1L-AS1 to function as a competitive endogenous RNA (ceRNA), sponging key microRNAs, such as miR-7a-5p, miR-101-3p, miR-181a-5p, and miR-27a-3p, thereby modulating oncogenes including EZH2, MCL1, and KRAS, which are linked to increased cancer cell survival, proliferation, and metastasis.

In addition to its role in TNBC, correlation analysis using breast cancer patient datasets revealed a significant association between LURAP1L-AS1 and ESR1 expression, suggesting its broader impact across breast cancer subtypes. Concordantly, LURAP1L-AS1 depletion inhibited estrogen receptor-positive (ER+) MCF7 breast cancer cells colony formation and organotypic growth.

Our findings establish LURAP1L-AS1 as a functional lncRNA that promotes breast cancer progression, highlighting its potential for use in RNA-based therapies for breast cancer.

长链非编码rna （lncRNAs）正在成为癌症生物学的关键调控因子，但它们在乳腺癌，特别是三阴性乳腺癌（TNBC）中的作用仍不完全清楚。通过针对MDA-MB-231和BT-549 TNBC细胞模型中TNBC相关lncrna的定制siRNA文库筛选，我们发现LURAP1L-AS1是TNBC进展的关键调节剂。TNBC患者的生存分析显示，LURAP1L-AS1表达升高与临床预后不良之间存在显著关联。LURAP1L-AS1敲低显著损害TNBC模型的集落形成和类器官生长，与细胞凋亡增加相关，从而突出其促进肿瘤发生的作用。对lurap1l - as1缺失细胞的RNA测序显示，与细胞增殖、凋亡、迁移和RNA加工相关的通路失调。生物信息学分析预测，LURAP1L-AS1作为竞争性内源性RNA （ceRNA）发挥作用，吞噬关键microrna，如miR-7a-5p、miR-101-3p、miR-181a-5p和miR-27a-3p，从而调节癌基因，包括EZH2、MCL1和KRAS，这些癌基因与癌细胞存活、增殖和转移增加有关。除了在TNBC中发挥作用外，使用乳腺癌患者数据集进行的相关分析显示，LURAP1L-AS1和ESR1表达之间存在显著关联，表明其在乳腺癌亚型中具有更广泛的影响。与此同时，LURAP1L-AS1缺失抑制雌激素受体阳性（ER+） MCF7乳腺癌细胞集落形成和器官型生长。我们的研究结果证实了LURAP1L-AS1是一种促进乳腺癌进展的功能性lncRNA，突出了其在基于rna的乳腺癌治疗中的潜力。

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引用次数: 0

Long noncoding RNA hottip maintained skeletal homeostasis via suppressing the enhancer of zeste homolog 2 (Ezh2)/histone methylation regulatory axis 长非编码 RNA hottip 通过抑制泽斯特同源增强子 2（Ezh2）/组蛋白甲基化调控轴维持骨骼稳态

IF 5.9 3区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Non-coding RNA Research

Pub Date : 2025-06-01 Epub Date: 2025-02-28 DOI: 10.1016/j.ncrna.2025.01.003

Zhi-Peng Li , Yong-Xin Mai , Shu-Ting Zhou , Chuan-jian Shi , Jiang Shao , Pu-ping Liang , Wei-cheng Liang , Jin-fang Zhang

Objective

Recent evidence underscores the pivotal role of long noncoding RNAs (lncRNAs) in orchestrating bone remodeling and skeletal homeostasis by harmonizing osteoblast and osteoclast development. Notably, the oncogenic lncRNA, Hottip, implicated in osteogenesis regulation, remains insufficiently elucidated. This study aims to delineate Hottip's role in bone remodeling and skeletal homeostasis.

Methods

Hottip knockout mice were generated to discern its impact on bone metabolism. In vitro experiments probed cellular mechanisms influenced by Hottip, while molecular interactions were explored to understand its basis. The therapeutic potential of Hottip overexpression was investigated through in vivo experiments.

Results

Hottip knockout mice displayed disrupted bone metabolism, aberrant tissue, and compromised quality, leading to delayed fracture healing. In vitro, Hottip knockdown impeded osteoblast differentiation, while promoting osteoclast differentiation, with converse effects upon Hottip overexpression. Mechanistically, Hottip physically interacted with EZH2, inducing its degradation and enhancing osteogenic gene transcription by suppressing H3K9me3 and H3K27me3. In vivo experiments validated Hottip overexpression's potential to promote bone regeneration and hasten fracture healing.

Conclusion

In summary, this study identifies Hottip as a critical regulator in osteoblast and osteoclast differentiation, crucial for maintaining skeletal homeostasis. Hottip emerges as a promising therapeutic target for enhancing bone regeneration. These findings contribute valuable insights into lncRNA-mediated mechanisms governing skeletal dynamics.

最近的证据强调了长链非编码rna （lncRNAs）通过协调成骨细胞和破骨细胞的发育在协调骨重塑和骨骼稳态中的关键作用。值得注意的是，与成骨调控有关的致癌lncRNA Hottip仍未得到充分阐明。本研究旨在描述Hottip在骨重塑和骨骼稳态中的作用。方法采用骨尖敲除小鼠，观察其对骨代谢的影响。体外实验探讨了Hottip对细胞的影响机制，并探讨了分子相互作用的基础。通过体内实验研究了Hottip过表达的治疗潜力。结果骨尖敲除小鼠表现出骨代谢紊乱、组织异常和质量下降，导致骨折愈合延迟。在体外，Hottip敲低抑制成骨细胞分化，同时促进破骨细胞分化，对Hottip过表达有相反的作用。机制上，Hottip与EZH2物理相互作用，诱导其降解，并通过抑制H3K9me3和H3K27me3促进成骨基因转录。体内实验证实了Hottip过表达促进骨再生和加速骨折愈合的潜力。综上所述，本研究确定Hottip是成骨细胞和破骨细胞分化的关键调节因子，对维持骨骼稳态至关重要。Hottip是一种很有前景的骨再生治疗靶点。这些发现为lncrna介导的骨骼动力学机制提供了有价值的见解。

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引用次数: 0

miR-135b: A key role in cancer biology and therapeutic targets miR-135b：在癌症生物学和治疗靶点中的关键作用

IF 5.9 3区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Non-coding RNA Research

Pub Date : 2025-06-01 Epub Date: 2025-02-20 DOI: 10.1016/j.ncrna.2025.02.005

Yingchun Shao , Shuangshuang Zhang , Yuxin Pan , Zhan Peng , Yinying Dong

miR-135b, a microRNA, is consistently up-regulated in various cancer tissues and cells, promoting cancer progression. By inhibiting one or more target genes, miR-135b regulates phenotypes such as cancer growth, apoptosis, migration, invasion, drug resistance, and angiogenesis, establishing it as a critical driver of cancer progression. Additionally, miR-135b is regulated by various oncogenes and therapeutic drugs, highlighting its complexity and therapeutic potential. Significant progress has been made in understanding miR-135b's impact on cancer cell behavior, establishing it as a promising biomarker for cancer diagnosis and prognosis, as well as a potential target for future cancer therapies. However, despite the extensive research on this topic, there has been no comprehensive review summarizing its role and mechanisms across different cancer types. This review aims to provide a detailed overview of the biological characteristics of miR-135b, its regulatory targets, upstream signaling pathways, and its therapeutic potential, including its influence on cancer chemoresistance. The review also addresses key controversies surrounding miR-135b in cancer research, aiming to deepen the understanding of its role, promote the transformation of its clinical application, and provide a theoretical foundation for developing more effective cancer treatment strategies.

miR-135b是一种microRNA，在各种癌症组织和细胞中持续上调，促进癌症进展。通过抑制一个或多个靶基因，miR-135b调节诸如肿瘤生长、凋亡、迁移、侵袭、耐药和血管生成等表型，使其成为癌症进展的关键驱动因素。此外，miR-135b受多种癌基因和治疗药物的调控，凸显了其复杂性和治疗潜力。在了解miR-135b对癌细胞行为的影响方面取得了重大进展，将其确定为癌症诊断和预后的有希望的生物标志物，以及未来癌症治疗的潜在靶点。然而，尽管对这一主题进行了广泛的研究，但尚未有全面的综述总结其在不同癌症类型中的作用和机制。本文旨在详细介绍miR-135b的生物学特性、调控靶点、上游信号通路及其治疗潜力，包括其对癌症化疗耐药的影响。本综述还针对miR-135b在癌症研究中的关键争议进行了梳理，旨在加深对其作用的认识，促进其临床应用的转变，为制定更有效的癌症治疗策略提供理论基础。

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