Molecular and Cellular Probes最新文献_第5页

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

Molecular and Cellular Probes

Pub 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。

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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

Molecular and Cellular Probes

Pub 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

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

Molecular and Cellular Probes

Pub 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。

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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

Molecular and Cellular Probes

Pub 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。

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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

Molecular and Cellular Probes

Pub 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。

{"title":"Serum vault RNA1-1 levels reflect blood cells and bone marrow","authors":"Yuki Hatayama , Hisashi Shimohiro , Yuki Hashimoto , Hitomi Ichikawa , Koji Kawamura , Toru Motokura","doi":"10.1016/j.mcp.2025.102018","DOIUrl":"10.1016/j.mcp.2025.102018","url":null,"abstract":"<div><h3>Introduction</h3><div>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).</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>The vtRNA1-1 levels in the blood of 11 patients with hematological disorders averaged 10.8 log<sub>10</sub> cps/ml, significantly higher than 8.4 log<sub>10</sub> 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.</div></div><div><h3>Conclusions</h3><div>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.</div></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"80 ","pages":"Article 102018"},"PeriodicalIF":2.3,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143383913","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

Molecular and Cellular Probes

Pub Date : 2025-02-01 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 , Kaixuan Wang , Jian Song , Zhuang Chen , Yongyu Li , 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

The application of CRISPR/Cas9–based genome-wide screening to disease research 基于CRISPR/ cas9的全基因组筛选在疾病研究中的应用

IF 2.3 3区生物学 Q3 BIOCHEMICAL RESEARCH METHODS

Molecular and Cellular Probes

Pub Date : 2025-02-01 DOI: 10.1016/j.mcp.2024.102004

Xiuqin Chen , Min Zheng , Su Lin , Meiqing Huang , Shaoying Chen , Shilong Chen

High-throughput genetic screening serves as an indispensable approach for deciphering gene functions and the intricate relationships between phenotypes and genotypes. The CRISPR/Cas9 system, with its ability to precisely edit genomes on a large scale, has revolutionized the field by enabling the construction of comprehensive genomic libraries. This technology has become a cornerstone for genome-wide screenings in disease research. This review offers a comprehensive examination of how CRISPR/Cas9-based genetic screening has been leveraged to uncover genes that play a role in disease mechanisms, focusing on areas such as cancer development and viral replication processes. The insights presented in this review hold promise for the development of novel therapeutic strategies and precision medicine approaches.

高通量遗传筛选是解读基因功能和表型与基因型之间复杂关系的重要手段。CRISPR/Cas9系统具有大规模精确编辑基因组的能力，通过构建全面的基因组文库，使该领域发生了革命性的变化。这项技术已经成为疾病研究中全基因组筛选的基石。这篇综述全面研究了基于CRISPR/ cas9的基因筛选如何被利用来发现在疾病机制中发挥作用的基因，重点关注癌症发展和病毒复制过程等领域。本综述提出的见解为开发新的治疗策略和精确医学方法提供了希望。

引用次数: 0

LncRNA TMC3-AS1 silence alleviates lipopolysaccharide-induced acute kidney injury by suppressing Wnt5a-mediated autophagy and pyroptosis pathway LncRNA TMC3-AS1沉默通过抑制wnt5a介导的自噬和焦亡途径减轻脂多糖诱导的急性肾损伤。

IF 2.3 3区生物学 Q3 BIOCHEMICAL RESEARCH METHODS

Molecular and Cellular Probes

Pub Date : 2025-02-01 DOI: 10.1016/j.mcp.2024.102006

Jing Guo , Rao Fu , Bo Zhao , Hongbo Li , Jundong Jiao

Long non-coding RNA TMC3-AS1 is identified to be upregulated by lipopolysaccharide (LPS) in inflammatory disease, but its role in acute kidney injury (AKI) is almost unknown. The study investigated the involvement of TMC3-AS1 in LPS-induced AKI and its downstream molecular regulatory mechanism. Our data suggested that knocking down TMC3-AS1 significantly reduced renal dysfunction, tissue inflammation and tissue damage in LPS-induced mice, and promoted cell viability, inhibited inflammation, apoptosis and necrosis in LPS-stimulated human renal tubular epithelial cells HK2. Meanwhile, silencing TMC3-AS1 decreased the expression levels of Wnt5a, Atg5, NLRP3 and cleaved caspase1 and the ratio of LC3II/LC3I, but elevated p62 level in vivo and in vitro, suggesting the inhibitory effect of TMC3-AS1 silence on Wnt5a signaling, autophagy, and pyroptosis. Mechanically, TMC3-AS1 upregulated the expression of WNT5A mRNA and Wnt5a protein through competitively binding with miR-148a-3p, thus elevating the expression levels of autophagy and pyroptosis-associated markers in LPS-induced HK2 cells. MiR-148a-3p mimic also exerted protective effects on LPS-treated HK2 cells, which was counteracted by overexpressing WNT5A or TMC3-AS1. Altogether, these findings reveal that TMC3-AS1 inhibition restrains LPS-triggered AKI progression through inactivating Wnt5a -mediated autophagy and pyroptosis pathway.

长链非编码RNA TMC3-AS1在炎症性疾病中被脂多糖（LPS）上调，但其在急性肾损伤（AKI）中的作用几乎未知。本研究探讨了TMC3-AS1参与lps诱导的AKI及其下游分子调控机制。我们的数据表明，敲低TMC3-AS1可显著减轻lps诱导小鼠的肾功能障碍、组织炎症和组织损伤，提高lps刺激的人肾小管上皮细胞HK2的细胞活力，抑制炎症、凋亡和坏死。同时，沉默TMC3-AS1可降低Wnt5a、Atg5、NLRP3和cleaved caspase1的表达水平及LC3II/LC3I比值，但提高体内外p62水平，提示沉默TMC3-AS1对Wnt5a信号通路、自噬和焦亡有抑制作用。机械上，TMC3-AS1通过与miR-148a-3p的竞争性结合上调WNT5A mRNA和WNT5A蛋白的表达，从而提高lps诱导的HK2细胞中自噬和热噬相关标志物的表达水平。MiR-148a-3p mimic对lps处理的HK2细胞也有保护作用，但这种作用会被过表达WNT5A或TMC3-AS1所抵消。总之，这些发现表明TMC3-AS1抑制通过灭活Wnt5a介导的自噬和焦亡途径抑制lps触发的AKI进展。

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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

Molecular and Cellular Probes

Pub Date : 2025-02-01 DOI: 10.1016/j.mcp.2025.102009

Gabriella Páll , Tamás Pándics , Erzsébet Pintér , Mária Kun , Anna Karoliny , Lajos A. Réthy

引用次数: 0

A comprehensive report of the clinical and mutational profiles of 30 Iranian malignant infantile osteopetrosis patients 30名伊朗恶性婴儿骨质疏松症患者的临床和突变概况的综合报告。

IF 2.3 3区生物学 Q3 BIOCHEMICAL RESEARCH METHODS

Molecular and Cellular Probes

Pub Date : 2025-02-01 DOI: 10.1016/j.mcp.2025.102014

Akbar Amirfiroozy , Maryam Naghinejad , Azim Rezamand , Hamid Farhangi , Zahra Golchehre , Hossein Jalali , Mohammad Taheri , Mohammad Keramatipour

Osteopetrosis is a group of genetically and clinically diverse inherited disorders characterized by an increase in bone density. The main known cause is an abnormality in the development or function of osteoclasts. Hence, the process of bone resorption is impaired, resulting in: 1- a reduction in bone marrow volume and, subsequently, a decrement in the hematopoietic capacity of bone marrow, which leads to anemia and compromised immunological function; 2- improper bone development, which leads to pressure on peripheral nerves, causing auditory, visual, and movement impairments; and 3- disturbance in the formation of bone microstructure that leads to susceptibility to bone fracture. This study aimed to evaluate the clinical symptoms and genetic causes of 30 patients (probands) who suffered from malignant infantile osteopetrosis, a subtype of this disorder. The Sanger sequencing technique was used to sequence four common genes (TCIRG1, CLCN7, SNX10, and OSTM1) in osteopetrosis. Subsequently, the selected variants were subjected to segregation analysis between the probands and their parents. Consequently, the sequencing of these four genes in probands revealed 16 pathogenic and likely pathogenic mutations, five of which had never been reported before. The TCIRG1 gene has three novel splice site variations and one frameshift variant. The CLCN7 gene had a novel missense variant. Also, a total of five variants of uncertain significance (VUSs) were identified in the analyzed sequences, of which three haven't been reported to date, and two were observed in osteopetrosis patients. Therefore, by documenting these novel likely pathogenic variants and VUS in known genes associated with this disease in patients, specialists can conduct more accurate genetic analysis and counseling when encountering these variants. Additionally, this documentation will facilitate the reclassification of these variants.

骨质疏松症是一组以骨密度增加为特征的遗传和临床多样化的遗传性疾病。已知的主要原因是破骨细胞发育或功能异常。因此，骨吸收过程受损，导致：1-骨髓体积减少，随后骨髓造血能力下降，导致贫血和免疫功能受损；2-骨骼发育不正常，导致周围神经受压，造成听觉、视觉和运动障碍；3-干扰骨微结构的形成，导致骨折易感性。本研究旨在评估30例患有恶性婴儿骨质疏松症（该疾病的一种亚型）的患者的临床症状和遗传原因。采用Sanger测序技术对骨质疏松症的四个常见基因（TCIRG1、CLCN7、SNX10和OSTM1）进行测序。随后，选择的变异进行先证者与其亲本之间的分离分析。因此，先证物中这4个基因的测序揭示了16个致病和可能致病的突变，其中5个以前从未报道过。TCIRG1基因有三个新的剪接位点变异和一个移码变异。CLCN7基因有一个新的错义变体。此外，在分析的序列中共鉴定出5个不确定意义变异（VUSs），其中3个尚未报道，2个在骨质疏松患者中观察到。因此，通过记录这些新的可能的致病变异和与患者疾病相关的已知基因中的VUS，专家可以在遇到这些变异时进行更准确的遗传分析和咨询。此外，本文档将有助于对这些变体进行重新分类。

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引用次数: 0