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Transcriptomic analysis of intracellular RNA granules and small extracellular vesicles: Unmasking their overlap in a cell model of Huntington's disease 细胞内RNA颗粒和细胞外小泡的转录组学分析:揭示它们在亨廷顿病细胞模型中的重叠。
IF 2.3 3区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-06-01 Epub Date: 2025-03-14 DOI: 10.1016/j.mcp.2025.102026
Deepti Kailash Nabariya , Lisa Maria Knüpfer , Patrick Hartwich , Manuela S. Killian , Florian Centler , Sybille Krauß
Huntington's disease (HD) arises from the abnormal expansion of a CAG repeat in the HTT gene. The mutant CAG repeat triggers aberrant RNA-protein interactions and translates into toxic aggregate-prone polyglutamine protein. These aberrant RNA-protein ineractions also seed the formation of cytoplasmic liquid-like granules, such as stress granules. Emerging evidence demonstrates that granules formed via liquid-liquid phase separation can mature into gel-like inclusions that persist within the cell and may act as precursor to aggregates that occur in patients' tissue. Thus, deregulation of RNA granules is an important component of neurodegeneration. Interestingly, both the formation of intracellular membrane-less organelles like stress granules and the secretion of small extracellular vesicles (sEVs) increase upon stress and under disease conditions. sEVs are lipid membrane-bound particles that are secreted from all cell types and may participate in the spreading of misfolded proteins and aberrant RNA-protein complexes across the central nervous system in neurodegenerative diseases like HD. In this study, we performed a comparative transcriptomic analysis of sEVs and RNA granules in an HD model. RNA granules and sEVs were isolated from an inducible HD cell model. Both sEVs and RNA granules were isolated from induced (HD) and non-induced (control) cells and analyzed by RNA sequencing. Our comparative analysis between the transcriptomics data of HD RNA granules and sEVs showed that: (I) intracellular RNA granules and extracellular RNA vesicles share content, (II) several non-coding RNAs translocate to RNA granules, and (III) the composition of RNA granules and sEVs is affected in HD cells. Our data showing common transcripts in intracellular RNA granules and extracellular sEVs suggest that formation of RNA granules and sEV loading may be related. Moreover, we found a high abundance of lncRNAs in both control and HD samples, with several transcripts under REST regulation, highlighting their potential role in HD pathogenesis and selective incorporation into sEVs. The transcriptome cargo of RNA granules or sEVs may serve as a source for diagnostic strategies. For example, disease-specific RNA-signatures of sEVs can serve as biomarker of central nervous system diseases. Therefore, we compared our dataset to transcriptomic data from HD patient sEVs in blood. However, our data suggest that the cell-type specific signature of sEV-secreted RNAs as well as their high variability may make it difficult to detect these biomarkers in blood.
亨廷顿氏病(HD)是由HTT基因中CAG重复序列的异常扩增引起的。突变的CAG重复序列触发异常的rna -蛋白相互作用,并转化为有毒的易聚集的聚谷氨酰胺蛋白。这些异常的rna -蛋白相互作用也为细胞质液体样颗粒的形成提供了种子,如应激颗粒。新出现的证据表明,通过液-液相分离形成的颗粒可以成熟为凝胶样的内含物,这些内含物可以在细胞内持续存在,并可能作为患者组织中聚集物的前体。因此,RNA颗粒的解除管制是神经变性的重要组成部分。有趣的是,在应激和疾病条件下,细胞内无膜细胞器(如应激颗粒)的形成和小细胞外囊泡(sev)的分泌都增加。sev是脂质膜结合颗粒,由所有细胞类型分泌,在HD等神经退行性疾病中可能参与错误折叠蛋白和异常rna -蛋白复合物在中枢神经系统的扩散。在这项研究中,我们在HD模型中对sev和RNA颗粒进行了比较转录组学分析。从诱导型HD细胞模型中分离到RNA颗粒和sev。从诱导细胞(HD)和非诱导细胞(对照)中分离sev和RNA颗粒,并通过RNA测序进行分析。我们对HD RNA颗粒和sev转录组学数据的比较分析表明:(I)细胞内RNA颗粒和细胞外RNA囊泡共享内容,(II)一些非编码RNA转运到RNA颗粒,(III) HD细胞中RNA颗粒和sev的组成受到影响。我们的数据显示细胞内RNA颗粒和细胞外sEV的共同转录本表明RNA颗粒的形成和sEV负载可能相关。此外,我们在对照和HD样本中都发现了高丰度的lncrna,其中有几个转录本受REST调控,这突出了它们在HD发病机制和选择性并入sev中的潜在作用。RNA颗粒或sev的转录组货物可以作为诊断策略的来源。例如,sev的疾病特异性rna标记可以作为中枢神经系统疾病的生物标志物。因此,我们将我们的数据集与HD患者血液中sev的转录组学数据进行了比较。然而,我们的数据表明,sev分泌的rna的细胞类型特异性特征以及它们的高变异性可能使得在血液中检测这些生物标志物变得困难。
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引用次数: 0
Silymarin plus doxorubicin exerts the anti-hepatocellular carcinoma effects via Wnt, apoptosis, autophagy and angiogenesis pathways 水飞蓟素联合阿霉素通过Wnt、凋亡、自噬和血管生成等途径发挥抗肝癌作用。
IF 2.3 3区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-06-01 Epub Date: 2025-03-04 DOI: 10.1016/j.mcp.2025.102022
Baohong Yuan , Ruotian Wang , Zehai Gao , Hameed Mirzeei , An-Dong Xiang , Feng Guo

Background

The biggest cause of death worldwide is liver cancer. Despite several initiatives and successes in treatment techniques, only a little improvement has been attained. In order to control this cancer, new therapeutic strategies are therefore required. Here, we evaluated the effects of doxorubicin and the milk thistle plant phytochemical Silymarin on liver cancer through apoptosis, autophagy, and Wnt signaling.

Methods

Silymarin both alone and together with doxorubicin was administered to induce cytotoxicity in the H22 cell line. qRT-PCR and Western blot analyses, the genes related to autophagy, Wnt signals, and cell death were examined.

Results

Doxorubicin and Silymarin both individually and combined dramatically slowed down H22 cells growth. Additionally, there was a significant drop in the Bcl-2 protein and a considerable rise in the caspase 8 and Bax proteins. LC3-I, LC3-II, and Beclin 1 have been all shown to be significantly elevated. Moreover, there was a substantial decrease in the expression of genes involved in the Wnt pathway, including cyclin D1, β-catenin, ZEB1, and Twist. The levels of AMPK were decreased in Silymarin with Doxorubicin alone and in combination, whereas VASP, VEGF, and HIF-1a were lowest.

Conclusion

Silymarin may enhance anti-tumor effects of doxorubicin through modulating autophagy, angiogenesis, and apoptosis, in-vitro.
背景:全世界最大的死亡原因是肝癌。尽管在治疗技术方面采取了一些举措并取得了成功,但只取得了一点改善。因此,为了控制这种癌症,需要新的治疗策略。在这里,我们评估了阿霉素和水飞蓟植物化学物质水飞蓟素通过凋亡、自噬和Wnt信号传导对肝癌的影响。方法:水飞蓟素单用及与阿霉素联用诱导H22细胞株细胞毒性。qRT-PCR和Western blot分析,检测自噬、Wnt信号和细胞死亡相关基因。结果:阿霉素和水飞蓟素单独或联合使用均能显著减缓H22细胞的生长。此外,Bcl-2蛋白显著下降,caspase 8和Bax蛋白显著升高。LC3-I、LC3-II和Beclin 1均明显升高。此外,参与Wnt通路的基因,包括cyclin D1、β-catenin、ZEB1和Twist的表达也大幅下降。水飞蓟素与阿霉素单独或联合使用时AMPK水平降低,而VASP、VEGF和HIF-1a水平最低。结论:水飞蓟素可能通过调节体外自噬、血管生成和细胞凋亡来增强阿霉素的抗肿瘤作用。
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引用次数: 0
Serum exosomal miR-454-3p contributes to malignant progression of lung cancer by inhibiting HHEX 血清外泌体miR-454-3p通过抑制HHEX参与肺癌的恶性进展。
IF 2.3 3区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-04-01 Epub Date: 2025-02-16 DOI: 10.1016/j.mcp.2025.102019
Gangqin Hu, Peng Cai, Jingjing Li, Liuyang Yu, Bolin Zhao, Guiming Chen

Background

Lung cancer is a common cancer. Exosomes are emerging mediators of intercellular communication, and miRNAs serve a crucial position in cancer progression. This project intends to discover whether exosomal miR-454-3p affects tumor progression and its underlying mechanisms.

Methods

Exosomes were isolated utilizing ultracentrifugation. The exosomal biomarkers level was monitored by western blot (WB). The miR-454-3p levels were assessed by quantitative reverse transcription polymerase chain reaction (qRT-PCR), and HHEX expression were detected by qRT-PCR and WB. Cell growth and metastasis were detected through CCK-8, colony formation assay and transwell. Meanwhile, the dual luciferase reporter system and immunoprecipitation (RIP) assay was applied to clarify the interactions between miR-454-3p and HHEX.

Results

We successfully isolated serum exosomes from NSCLC patients. Then, our team discovered that miR-454-3p was elevated in serum-derived exosomes from NSCLC patients. Functional analysis disclosed that exosomes accelerated NSCLC cell proliferation and metastasis. Silencing of exosomal miR-454-3p hindered NSCLC cell proliferation and metastasis. Subsequently, the starbase database declared that miR-454-3p was interacted with HHEX. HHEX overexpression reversed the promotion of NSCLC cell proliferation and metastasis by exosomal miR-454-3p.

Conclusions

Exosomal miR-454-3p enhanced the progression of NSCLC cells through HHEX. miR-454-3p may be a therapeutic target for NSCLC.
背景:肺癌是一种常见的癌症。外泌体是细胞间通讯的新兴介质,mirna在癌症进展中起着至关重要的作用。本项目旨在发现外泌体miR-454-3p是否影响肿瘤进展及其潜在机制。方法:采用超离心分离外泌体。western blot (WB)检测外泌体生物标志物水平。采用定量逆转录聚合酶链反应(qRT-PCR)检测miR-454-3p水平,采用qRT-PCR和WB检测HHEX表达。通过CCK-8、集落形成试验和transwell检测细胞生长和转移情况。同时,采用双荧光素酶报告系统和免疫沉淀(RIP)实验来阐明miR-454-3p与HHEX之间的相互作用。结果:我们成功地分离了非小细胞肺癌患者的血清外泌体。然后,我们的团队发现miR-454-3p在非小细胞肺癌患者血清来源的外泌体中升高。功能分析显示外泌体加速了NSCLC细胞的增殖和转移。外泌体miR-454-3p的沉默抑制了NSCLC细胞的增殖和转移。随后,starbase数据库宣布miR-454-3p与HHEX相互作用。HHEX过表达逆转外泌体miR-454-3p对NSCLC细胞增殖和转移的促进作用。结论:外泌体miR-454-3p通过HHEX促进NSCLC细胞的进展。miR-454-3p可能是NSCLC的治疗靶点。
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引用次数: 0
Serum vault RNA1-1 levels reflect blood cells and bone marrow 血清穹窿RNA1-1水平反映血细胞和骨髓。
IF 2.3 3区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-04-01 Epub Date: 2025-02-12 DOI: 10.1016/j.mcp.2025.102018
Yuki Hatayama , Hisashi Shimohiro , Yuki Hashimoto , Hitomi Ichikawa , Koji Kawamura , Toru Motokura

Introduction

Vault RNA1-1 (vtRNA1-1) exhibits antiviral and anti-apoptotic effects in infected and malignant cells. We observed that vtRNA1-1 levels in serum fluctuate in patients with hematological disorders, but its extracellular functions remain unclear. This study evaluates the potential of serum vtRNA1-1 levels as a biomarker for hematological disorders and investigates its association with bone marrow cell density (BMC).

Methods

Blood and serum samples were collected from patients with hematological disorders, patients who underwent bone marrow examination, PBSCT donors, and AML patients who received chemotherapy. VtRNA1-1 levels were measured using real-time quantitative RT-PCR. BMC was calculated by digital image analysis, and multiple regression analysis was performed using serum vtRNA1-1 and hematological and biochemical data as explanatory variables.

Results

The vtRNA1-1 levels in the blood of 11 patients with hematological disorders averaged 10.8 log10 cps/ml, significantly higher than 8.4 log10 cps/ml in serum. Multiple regression analysis estimated the vtRNA1-1 expression levels of each blood cell. In 87 patients who underwent bone marrow examination, there was a significant correlation between serum vtRNA1-1 levels and BMC (Rs = 0.24, P = 0.023). In PBSCT donors, serum vtRNA1-1 levels increased after G-CSF administration (P < 0.001), and in AML patients, serum vtRNA1-1 levels decreased after the initiation of chemotherapy, fluctuating in parallel with white blood cell counts.

Conclusions

Our findings suggest that serum vtRNA1-1, derived from peripheral blood and bone marrow cells, can potentially serve as a clinical biomarker in specific diseases.
Vault RNA1-1 (vtRNA1-1)在感染和恶性细胞中表现出抗病毒和抗凋亡作用。我们观察到血液病患者血清中vtrna -1水平波动,但其细胞外功能尚不清楚。本研究评估了血清vtRNA1-1水平作为血液学疾病生物标志物的潜力,并探讨了其与骨髓细胞密度(BMC)的关系。方法:采集血液病患者、骨髓检查患者、PBSCT供者和化疗AML患者的血液和血清样本。实时定量RT-PCR检测vtrna -1水平。通过数字图像分析计算BMC,并以血清vtrna -1和血液学生化数据作为解释变量进行多元回归分析。结果:11例血液病患者血液中vtrna -1水平平均为10.8 log10 cps/ml,显著高于血清中的8.4 log10 cps/ml。多元回归分析估计各血细胞vtrna -1表达水平。87例患者行骨髓检查,血清vtrna -1水平与BMC有显著相关性(Rs=0.24, P=0.023)。在给予G-CSF后,PBSCT供者血清vtRNA1-1水平升高(结论:我们的研究结果表明,来自外周血和骨髓细胞的血清vtRNA1-1可能作为特定疾病的临床生物标志物。
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引用次数: 0
The role of APOA1-AS in colorectal cancer: Investigating its association with malignant biological behaviors APOA1-AS 在结直肠癌中的作用:研究其与恶性生物学行为的关系
IF 2.3 3区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-04-01 Epub Date: 2025-02-16 DOI: 10.1016/j.mcp.2025.102017
Gang Liu , Qin Zhao , Yan Li , Dongmei Zhu , Hong Peng

Purpose

Colorectal cancer (CRC) is a common malignant tumor associated with high morbidity and mortality. Long non-coding RNAs (lncRNAs) play crucial roles in cancer development and progression. This study aimed to explore the role of lncRNA APOA1-AS in colorectal cancer and elucidate its underlying mechanisms.

Methods

Clinical samples were collected, and high-throughput sequencing was performed to identify differentially expressed lncRNAs in colorectal cancer. Among these, the key lncRNA APOA1-AS was selected for further investigation. The expression of APOA1-AS in colorectal cancer tissues and cells was evaluated. The effects of APOA1-AS on cell proliferation, migration, invasion, and apoptosis were assessed through knockdown and overexpression of APOA1-AS in SW620 and RKO cells. Additionally, the relationship between APOA1-AS and the malignant biological behaviors of colorectal cancer cells was also investigated. Furthermore, the involvement of APOA1-AS in glucose metabolism reprogramming and the cGMP-PKG signaling pathway was analyzed.

Results

A total of 2985 differentially expressed lncRNAs were identified in colorectal cancer, including APOA1-AS, which showed the most significant upregulation. APOA1-AS expression was significantly higher in colorectal cancer tissues compared to normal tissues. Overexpression of APOA1-AS promoted cell proliferation, migration, and invasion while inhibiting apoptosis in SW620 and RKO cells. Furthermore, APOA1-AS was found to regulate glucose metabolism reprogramming, enhance tumor malignant biological behaviors and facilitate tumor cell drug resistance through the cGMP-PKG signaling pathway.

Conclusion

Our study demonstrates that APOA1-AS is a potential key regulator in colorectal cancer development and progression. It functions via glucose metabolism reprogramming and the cGMP-PKG signaling pathway, offering a novel therapeutic target for colorectal cancer.
目的:结直肠癌(Colorectal cancer, CRC)是一种常见的高发病率和高死亡率的恶性肿瘤。长链非编码rna (lncRNAs)在癌症的发生和发展中起着至关重要的作用。本研究旨在探讨lncRNA APOA1-AS在结直肠癌中的作用,并阐明其潜在机制。方法:收集临床样本,进行高通量测序,鉴定结直肠癌中差异表达的lncrna。其中选择关键lncRNA APOA1-AS进行进一步研究。测定APOA1-AS在结直肠癌组织和细胞中的表达。通过在SW620和RKO细胞中下调和过表达APOA1-AS,评估APOA1-AS对细胞增殖、迁移、侵袭和凋亡的影响。此外,我们还研究了APOA1-AS与结直肠癌细胞恶性生物学行为的关系。进一步分析了APOA1-AS在糖代谢重编程和cGMP-PKG信号通路中的作用。结果:在结直肠癌中共鉴定出2985个差异表达的lncrna,其中APOA1-AS表达上调最为显著。APOA1-AS在结直肠癌组织中的表达明显高于正常组织。在SW620和RKO细胞中,APOA1-AS过表达促进细胞增殖、迁移和侵袭,同时抑制细胞凋亡。此外,APOA1-AS通过cGMP-PKG信号通路调节糖代谢重编程,增强肿瘤恶性生物学行为,促进肿瘤细胞耐药。结论:我们的研究表明APOA1-AS是结直肠癌发生发展的潜在关键调控因子。它通过糖代谢重编程和cGMP-PKG信号通路发挥作用,为结直肠癌的治疗提供了新的靶点。
{"title":"The role of APOA1-AS in colorectal cancer: Investigating its association with malignant biological behaviors","authors":"Gang Liu ,&nbsp;Qin Zhao ,&nbsp;Yan Li ,&nbsp;Dongmei Zhu ,&nbsp;Hong Peng","doi":"10.1016/j.mcp.2025.102017","DOIUrl":"10.1016/j.mcp.2025.102017","url":null,"abstract":"<div><h3>Purpose</h3><div>Colorectal cancer (CRC) is a common malignant tumor associated with high morbidity and mortality. Long non-coding RNAs (lncRNAs) play crucial roles in cancer development and progression. This study aimed to explore the role of lncRNA APOA1-AS in colorectal cancer and elucidate its underlying mechanisms.</div></div><div><h3>Methods</h3><div>Clinical samples were collected, and high-throughput sequencing was performed to identify differentially expressed lncRNAs in colorectal cancer. Among these, the key lncRNA APOA1-AS was selected for further investigation. The expression of APOA1-AS in colorectal cancer tissues and cells was evaluated. The effects of APOA1-AS on cell proliferation, migration, invasion, and apoptosis were assessed through knockdown and overexpression of APOA1-AS in SW620 and RKO cells. Additionally, the relationship between APOA1-AS and the malignant biological behaviors of colorectal cancer cells was also investigated. Furthermore, the involvement of APOA1-AS in glucose metabolism reprogramming and the cGMP-PKG signaling pathway was analyzed.</div></div><div><h3>Results</h3><div>A total of 2985 differentially expressed lncRNAs were identified in colorectal cancer, including APOA1-AS, which showed the most significant upregulation. APOA1-AS expression was significantly higher in colorectal cancer tissues compared to normal tissues. Overexpression of APOA1-AS promoted cell proliferation, migration, and invasion while inhibiting apoptosis in SW620 and RKO cells. Furthermore, APOA1-AS was found to regulate glucose metabolism reprogramming, enhance tumor malignant biological behaviors and facilitate tumor cell drug resistance through the cGMP-PKG signaling pathway.</div></div><div><h3>Conclusion</h3><div>Our study demonstrates that APOA1-AS is a potential key regulator in colorectal cancer development and progression. It functions via glucose metabolism reprogramming and the cGMP-PKG signaling pathway, offering a novel therapeutic target for colorectal cancer.</div></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"80 ","pages":"Article 102017"},"PeriodicalIF":2.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Clinical significance analysis of microRNA-199a-3p in gingival crevicular fluid for patients with chronic periodontitis 龈沟液微量rna -199a-3p在慢性牙周炎患者中的临床意义分析。
IF 2.3 3区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-04-01 Epub Date: 2025-02-12 DOI: 10.1016/j.mcp.2025.102015
Kaixuan Yan, Yu Zheng, Jing Liu, Shuo Li, Wei Si

Objective

The aim was to investigate the clinical performance of microRNA-199a-3p (miR-199a-3p) in patients with chronic periodontitis.

Methods

91 patients with chronic periodontitis and 78 healthy individuals were enrolled for the research subjects. MiR-199a-3p expression was detected using real-time quantitative PCR (RT-qPCR) assay. Pearson correlation analysis was used for the relevance of miR-199a-3p with inflammatory mediators. Receiver operating characteristic (ROC) and logistic regression were conducted for the evaluation of the diagnostic performance and risk factors of chronic periodontitis. Bioinformatics analysis was utilized for miR-199a-3p-related genes.

Results

MiR-199a-3p was distinctly decreased in gingival crevicular fluid from patients with chronic periodontitis. The area under the curve (AUC) was 0.978 to discriminate chronic periodontitis patients from healthy individuals. The negative correlation was observed between miR-199a-3p and inflammatory factors. Logistic regression showed that miR-199a-3p was an independently protective factor for the occurrence of chronic periodontitis. Bioinformatics analysis revealed that the predictive regulated genes of miR-199a-3p mainly concentrated in inflammatory-associated signaling pathways.

Conclusion

MiR-199a-3p was attenuated in patients with chronic periodontitis and an underlying diagnostic biomarker for the disease.
目的:探讨microRNA-199a-3p (miR-199a-3p)在慢性牙周炎患者中的临床表现。方法:91例慢性牙周炎患者和78名健康者作为研究对象。采用实时定量PCR (RT-qPCR)检测MiR-199a-3p的表达。采用Pearson相关分析miR-199a-3p与炎症介质的相关性。采用受试者工作特征(ROC)和logistic回归对慢性牙周炎的诊断效果和危险因素进行评价。对mir -199a-3p相关基因进行生物信息学分析。结果:慢性牙周炎患者龈沟液中MiR-199a-3p明显降低。曲线下面积(AUC)为0.978,用于慢性牙周炎患者与健康人群的鉴别。miR-199a-3p与炎症因子呈负相关。Logistic回归分析显示,miR-199a-3p是慢性牙周炎发生的独立保护因素。生物信息学分析显示miR-199a-3p的预测性调控基因主要集中在炎症相关的信号通路中。结论:MiR-199a-3p在慢性牙周炎患者和该疾病的潜在诊断生物标志物中减弱。
{"title":"Clinical significance analysis of microRNA-199a-3p in gingival crevicular fluid for patients with chronic periodontitis","authors":"Kaixuan Yan,&nbsp;Yu Zheng,&nbsp;Jing Liu,&nbsp;Shuo Li,&nbsp;Wei Si","doi":"10.1016/j.mcp.2025.102015","DOIUrl":"10.1016/j.mcp.2025.102015","url":null,"abstract":"<div><h3>Objective</h3><div>The aim was to investigate the clinical performance of microRNA-199a-3p (miR-199a-3p) in patients with chronic periodontitis.</div></div><div><h3>Methods</h3><div>91 patients with chronic periodontitis and 78 healthy individuals were enrolled for the research subjects. MiR-199a-3p expression was detected using real-time quantitative PCR (RT-qPCR) assay. Pearson correlation analysis was used for the relevance of miR-199a-3p with inflammatory mediators. Receiver operating characteristic (ROC) and logistic regression were conducted for the evaluation of the diagnostic performance and risk factors of chronic periodontitis. Bioinformatics analysis was utilized for miR-199a-3p-related genes.</div></div><div><h3>Results</h3><div>MiR-199a-3p was distinctly decreased in gingival crevicular fluid from patients with chronic periodontitis. The area under the curve (AUC) was 0.978 to discriminate chronic periodontitis patients from healthy individuals. The negative correlation was observed between miR-199a-3p and inflammatory factors. Logistic regression showed that miR-199a-3p was an independently protective factor for the occurrence of chronic periodontitis. Bioinformatics analysis revealed that the predictive regulated genes of miR-199a-3p mainly concentrated in inflammatory-associated signaling pathways.</div></div><div><h3>Conclusion</h3><div>MiR-199a-3p was attenuated in patients with chronic periodontitis and an underlying diagnostic biomarker for the disease.</div></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"80 ","pages":"Article 102015"},"PeriodicalIF":2.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Clinical value of microRNA-4449 of non-small cell lung cancer patients undergoing thoracic paravertebral block thoracotomy microRNA-4449在非小细胞肺癌胸椎旁阻滞开胸术中的临床价值
IF 2.3 3区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-04-01 Epub Date: 2025-03-01 DOI: 10.1016/j.mcp.2025.102020
Yu Sun , Jiantao Zhang , Licai Zhang , Liquan Qiu , Huayi Zhang

Objective

The aim of this study was to investigate the clinical significance of microRNA-4449 (miR-4449) in patients attacked by non-small cell lung cancer (NSCLC) undergoing thoracic paravertebral block (TPVB) thoracotomy.

Methods

A total of 122 patients diagnosed with NSCLC and 101 healthy individuals were recruited in this case-control study. Quantitative real-time polymerase reaction time (qRT-PCR) assay was applied to quantify the serum levels of miR-4449 in all participants. To assess the diagnostic potential of miR-4449, receiver operating characteristic (ROC) curves were constructed. Additionally, the prognostic value of miR-4449 was evaluated using Kaplan-Meier method and Cox regression analyses. The possible target genes and related proteins of miR-4449 were predicted via bioinformatics analysis.

Results

MiR-4449 expression was notably reduced in NSCLC patients relative to healthy volunteers (P < 0.001), with the area under the curve (AUC) reaching 0.952, demonstrating its ability to effectively differentiate between NSCLC patients and healthy individuals. Serum levels of miR-4449 were negatively in relation to tumor node metastasis stage and lymph node metastasis (P < 0.05). Moreover, a significant increase in miR-4449 expression was observed in patients following TPVB thoracotomy, as compared to pre-operative levels (P < 0.001). The AUC of 0.884 further highlighted its potential to distinguish between the effective group and the invalid group. Notably, patients expressing high levels of miR-4449 exhibited improved overall survival (P < 0.001), and miR-4449 (P < 0.001, HR = 2.290, 95 % = 1.450–3.615) was identified as an independently prognostic predictor for NSCLC. Bioinformatics analysis of miR-4999 target genes revealed key tumor-associated pathways and proteins, offering valuable insights into its molecular mechanisms in NSCLC.

Conclusion

Serum levels of miR-4449 were significantly decreased in patients with NSCLC and exhibited a correlation with the severity of the tumor. Furthermore, miR-4449 emerged as a potential prognostic biomarker, offering valuable insight into the clinical outcome for NSCLC undergoing TPVB thoracotomy.
研究目的本研究旨在探讨接受胸椎旁阻滞(TPVB)开胸手术的非小细胞肺癌(NSCLC)患者体内microRNA-4449(miR-4449)的临床意义:这项病例对照研究共招募了 122 名确诊为 NSCLC 的患者和 101 名健康人。采用实时定量聚合酶反应时间(qRT-PCR)测定所有参与者血清中的 miR-4449 水平。为了评估 miR-4449 的诊断潜力,研究人员绘制了接收者操作特征曲线(ROC)。此外,还使用 Kaplan-Meier 法和 Cox 回归分析评估了 miR-4449 的预后价值。通过生物信息学分析预测了miR-4449可能的靶基因和相关蛋白:结果:与健康志愿者相比,NSCLC 患者的 miR-4449 表达明显降低(PC结论:血清中 miR-4449 的水平在 NSCLC 患者中明显降低:NSCLC患者血清中的miR-4449水平明显下降,并与疾病的严重程度相关。此外,miR-4449还是一种潜在的预后生物标志物,为了解接受TPVB开胸手术的NSCLC患者的临床预后提供了有价值的信息。
{"title":"Clinical value of microRNA-4449 of non-small cell lung cancer patients undergoing thoracic paravertebral block thoracotomy","authors":"Yu Sun ,&nbsp;Jiantao Zhang ,&nbsp;Licai Zhang ,&nbsp;Liquan Qiu ,&nbsp;Huayi Zhang","doi":"10.1016/j.mcp.2025.102020","DOIUrl":"10.1016/j.mcp.2025.102020","url":null,"abstract":"<div><h3>Objective</h3><div>The aim of this study was to investigate the clinical significance of microRNA-4449 (miR-4449) in patients attacked by non-small cell lung cancer (NSCLC) undergoing thoracic paravertebral block (TPVB) thoracotomy.</div></div><div><h3>Methods</h3><div>A total of 122 patients diagnosed with NSCLC and 101 healthy individuals were recruited in this case-control study. Quantitative real-time polymerase reaction time (qRT-PCR) assay was applied to quantify the serum levels of miR-4449 in all participants. To assess the diagnostic potential of miR-4449, receiver operating characteristic (ROC) curves were constructed. Additionally, the prognostic value of miR-4449 was evaluated using Kaplan-Meier method and Cox regression analyses. The possible target genes and related proteins of miR-4449 were predicted via bioinformatics analysis.</div></div><div><h3>Results</h3><div>MiR-4449 expression was notably reduced in NSCLC patients relative to healthy volunteers (<em>P</em> &lt; 0.001), with the area under the curve (AUC) reaching 0.952, demonstrating its ability to effectively differentiate between NSCLC patients and healthy individuals. Serum levels of miR-4449 were negatively in relation to tumor node metastasis stage and lymph node metastasis (<em>P</em> &lt; 0.05). Moreover, a significant increase in miR-4449 expression was observed in patients following TPVB thoracotomy, as compared to pre-operative levels (<em>P</em> &lt; 0.001). The AUC of 0.884 further highlighted its potential to distinguish between the effective group and the invalid group. Notably, patients expressing high levels of miR-4449 exhibited improved overall survival (<em>P</em> &lt; 0.001), and miR-4449 (<em>P</em> &lt; 0.001, HR = 2.290, 95 % = 1.450–3.615) was identified as an independently prognostic predictor for NSCLC. Bioinformatics analysis of miR-4999 target genes revealed key tumor-associated pathways and proteins, offering valuable insights into its molecular mechanisms in NSCLC.</div></div><div><h3>Conclusion</h3><div>Serum levels of miR-4449 were significantly decreased in patients with NSCLC and exhibited a correlation with the severity of the tumor. Furthermore, miR-4449 emerged as a potential prognostic biomarker, offering valuable insight into the clinical outcome for NSCLC undergoing TPVB thoracotomy.</div></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"80 ","pages":"Article 102020"},"PeriodicalIF":2.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143473049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Corrigendum to “Identification of circRNA-mediated competing endogenous RNA network involved in the development of cervical cancer” [Mol. Cell. Probes. 78 (2024) 101984] “circrna介导的内源性竞争性RNA网络参与宫颈癌发展的鉴定”的勘误表[Mol. Cell.]。探测器。78(2024)101984]。
IF 2.3 3区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-04-01 Epub Date: 2025-03-07 DOI: 10.1016/j.mcp.2025.102021
Shaosheng Lou , Wang Yang , Qian Zhao , Yunshan Ouyang , Lingling Cao , Chen Lin
{"title":"Corrigendum to “Identification of circRNA-mediated competing endogenous RNA network involved in the development of cervical cancer” [Mol. Cell. Probes. 78 (2024) 101984]","authors":"Shaosheng Lou ,&nbsp;Wang Yang ,&nbsp;Qian Zhao ,&nbsp;Yunshan Ouyang ,&nbsp;Lingling Cao ,&nbsp;Chen Lin","doi":"10.1016/j.mcp.2025.102021","DOIUrl":"10.1016/j.mcp.2025.102021","url":null,"abstract":"","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"80 ","pages":"Article 102021"},"PeriodicalIF":2.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143587914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
THBS1 knockdown suppresses pancreatic cancer progression through JAK2/STAT3 signaling pathway THBS1敲低通过JAK2/STAT3信号通路抑制胰腺癌进展
IF 2.3 3区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-02-01 Epub Date: 2024-12-26 DOI: 10.1016/j.mcp.2024.102003
Ping Li , Kaixuan Wang , Jian Song , Zhuang Chen , Yongyu Li , Zhaowei Chen

Background

Thrombospondin 1 (THBS1), a secreted protein, is implicated in the progression of numerous cancers, yet its specific contributions to pancreatic cancer (PC) remain underexplored.

Methods

The association between THBS1 levels and prognosis in PC was investigated. Functional experiments in vitro were used to determine the cell functions of siTHBS1 through CCK8 assay for cell proliferation, Muse® Cell Analyzer for apoptosis, and transwell assay for invasion and migration. Colivelin was applied in recovery experiment to investigate the mechanism of THBS1 regulating the JAK2/STAT3 pathway in BXPC-3 cell. In addition, the LV-shTHBS1 lentivirus was used to construct subcutaneous tumors in nude mice to verify the function of THBS1 in vivo.

Results

THBS1 expression was elevated in PC and associated with a poorer prognosis. THBS1 was highly expressed in these PC cells. siTHBS1 repressed cell growth, migration and invasiveness, while promoting apoptosis of BXPC-3 cells. THBS1 suppression also led to a decrease in the phosphorylation of JAK2 and STAT3. JAK2/STAT3 signaling activator (Colivelin) could partially reverse the biological effects. In addition, shTHBS1 can suppress the growth of implanted tumors in nude mice.

Conclusions

THBS1 knockdown suppressed cell proliferation, migration, and invasion while enhanced cell apoptosis through the JAK2/STAT3 signaling pathway.
背景:血栓反应蛋白1 (THBS1)是一种分泌蛋白,与许多癌症的进展有关,但其对胰腺癌(PC)的特异性贡献仍未得到充分研究。方法:探讨原发性肝癌患者THBS1水平与预后的关系。体外功能实验通过CCK8法检测细胞增殖,Muse®细胞分析仪检测细胞凋亡,transwell法检测细胞侵袭和迁移,检测siTHBS1的细胞功能。利用Colivelin进行恢复实验,探讨THBS1调控BXPC-3细胞JAK2/STAT3通路的机制。此外,我们利用LV-shTHBS1慢病毒在裸鼠体内构建皮下肿瘤,验证THBS1在体内的功能。结果:THBS1在PC中表达升高,预后较差。THBS1在这些PC细胞中高表达。siTHBS1抑制BXPC-3细胞的生长、迁移和侵袭,同时促进BXPC-3细胞的凋亡。THBS1抑制也导致JAK2和STAT3磷酸化水平降低。JAK2/STAT3信号激活因子Colivelin可以部分逆转生物学效应。此外,shTHBS1还能抑制裸鼠植入式肿瘤的生长。结论:THBS1敲低可通过JAK2/STAT3信号通路抑制细胞增殖、迁移和侵袭,同时增强细胞凋亡。
{"title":"THBS1 knockdown suppresses pancreatic cancer progression through JAK2/STAT3 signaling pathway","authors":"Ping Li ,&nbsp;Kaixuan Wang ,&nbsp;Jian Song ,&nbsp;Zhuang Chen ,&nbsp;Yongyu Li ,&nbsp;Zhaowei Chen","doi":"10.1016/j.mcp.2024.102003","DOIUrl":"10.1016/j.mcp.2024.102003","url":null,"abstract":"<div><h3>Background</h3><div>Thrombospondin 1 (THBS1), a secreted protein, is implicated in the progression of numerous cancers, yet its specific contributions to pancreatic cancer (PC) remain underexplored.</div></div><div><h3>Methods</h3><div>The association between THBS1 levels and prognosis in PC was investigated. Functional experiments <em>in vitro</em> were used to determine the cell functions of siTHBS1 through CCK8 assay for cell proliferation, Muse® Cell Analyzer for apoptosis, and transwell assay for invasion and migration. Colivelin was applied in recovery experiment to investigate the mechanism of THBS1 regulating the JAK2/STAT3 pathway in BXPC-3 cell. In addition, the LV-shTHBS1 lentivirus was used to construct subcutaneous tumors in nude mice to verify the function of THBS1 <em>in vivo</em>.</div></div><div><h3>Results</h3><div>THBS1 expression was elevated in PC and associated with a poorer prognosis. THBS1 was highly expressed in these PC cells. siTHBS1 repressed cell growth, migration and invasiveness, while promoting apoptosis of BXPC-3 cells. THBS1 suppression also led to a decrease in the phosphorylation of JAK2 and STAT3. JAK2/STAT3 signaling activator (Colivelin) could partially reverse the biological effects. In addition, shTHBS1 can suppress the growth of implanted tumors in nude mice.</div></div><div><h3>Conclusions</h3><div>THBS1 knockdown suppressed cell proliferation, migration, and invasion while enhanced cell apoptosis through the JAK2/STAT3 signaling pathway.</div></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"79 ","pages":"Article 102003"},"PeriodicalIF":2.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142878328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Uncovering molecular sensitization patterns for peanut in East-Central European children: The dominance of Ara h 6 揭示花生在中东欧儿童中的分子致敏模式:Ara h6的优势。
IF 2.3 3区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-02-01 Epub Date: 2025-01-18 DOI: 10.1016/j.mcp.2025.102009
Gabriella Páll , Tamás Pándics , Erzsébet Pintér , Mária Kun , Anna Karoliny , Lajos A. Réthy
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引用次数: 0
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Molecular and Cellular Probes
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