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High expression of ARPC1B promotes the proliferation and apoptosis of clear cell renal cell carcinoma cells, leading to a poor prognosis ARPC1B的高表达促进透明细胞肾细胞癌细胞的增殖和凋亡,导致预后不良。
IF 2.3 3区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-02-01 DOI: 10.1016/j.mcp.2025.102011
Hongbo Wang , Zhendong Liu , Yuelin Du , Xingbo Cheng , Shanjun Gao , Wenjia Liang , Qingyun Zhu , Zhengfa Jiang , Yanzheng Gao , Panfeng Shang

Background

ARPC1B has been identified as a key regulator of malignant biological behavior in various tumors. However, its specific role in clear cell renal cell carcinoma (ccRCC) remains poorly understood. This study aims to evaluate the influence of ARPC1B on the prognosis and disease progression in ccRCC patients.

Methods

Multi-omics data and clinical information from public databases were analyzed to determine the associations between ARPC1B and prognosis, clinical features, immune microenvironment, and drug sensitivity in ccRCC. Co-expression and gene set enrichment analyses were conducted to elucidate the potential role of ARPC1B in ccRCC pathogenesis. Functional assays, including RT-qPCR, CCK8 assays, colony formation assays, immunofluorescence, immunohistochemistry, and xenograft tumor formation in nude mice, were performed to assess ARPC1B's impact on cell proliferation and apoptosis. Flow cytometry and Western blotting were further employed to investigate the underlying molecular mechanisms of ARPC1B in ccRCC.

Results

ARPC1B expression was significantly elevated in ccRCC and associated with an unfavorable prognosis. Both independent and meta-analyses confirmed that ARPC1B is an independent prognostic risk factor in ccRCC. Furthermore, ARPC1B expression significantly correlated with the immune microenvironment and drug sensitivity. In vitro, experiments demonstrated that ARPC1B knockdown suppressed ccRCC cell proliferation and induced apoptosis through the BAX-Bcl-2/c-caspase3/c-PARP axis, which was further validated by in vivo studies.

Conclusion

ARPC1B overexpression is associated with poor prognosis, altered immune status, and drug sensitivity in ccRCC. Furthermore, ARPC1B promotes the malignant behavior of ccRCC cells and holds potential as a prognostic biomarker and therapeutic target for ccRCC.
背景:ARPC1B已被确定为多种肿瘤恶性生物学行为的关键调节因子。然而,其在透明细胞肾细胞癌(ccRCC)中的具体作用仍知之甚少。本研究旨在评估ARPC1B对ccRCC患者预后和疾病进展的影响。方法:分析多组学数据和公共数据库的临床信息,确定ARPC1B与ccRCC患者预后、临床特征、免疫微环境和药物敏感性的关系。通过共表达和基因集富集分析来阐明ARPC1B在ccRCC发病机制中的潜在作用。通过RT-qPCR、CCK8测定、集落形成测定、免疫荧光、免疫组织化学和裸鼠异种移植肿瘤形成等功能分析来评估ARPC1B对细胞增殖和凋亡的影响。通过流式细胞术和Western blotting进一步研究ARPC1B在ccRCC中的潜在分子机制。结果:ARPC1B在ccRCC中表达显著升高,且与不良预后相关。独立分析和荟萃分析均证实ARPC1B是ccRCC的独立预后危险因素。此外,ARPC1B表达与免疫微环境和药物敏感性显著相关。体外实验表明,ARPC1B敲低可通过BAX-Bcl-2/c-caspase3/c-PARP轴抑制ccRCC细胞增殖并诱导凋亡,体内实验进一步验证了这一结论。结论:ARPC1B过表达与ccRCC患者预后不良、免疫状态改变及药物敏感性相关。此外,ARPC1B促进ccRCC细胞的恶性行为,并具有作为ccRCC预后生物标志物和治疗靶点的潜力。
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引用次数: 0
Targeting the HLC-1, LC-2/ad, and PC-14 lung cancer cell lines by the silver nanoparticles green-formulated by Descurainia sophia leaf extract 以Descurainia sophia叶提取物绿色配制的银纳米粒子靶向HLC-1、LC-2/ad和PC-14肺癌细胞株。
IF 2.3 3区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-02-01 DOI: 10.1016/j.mcp.2024.102001
Jianjun Ge, Jianbo Wen, Mingjun Jiang, Kefeng Huang, Saichun Qi, Wei Huang, Linlin Tan
Descurainia sophia, as an an ethno-medicinal plant, contains antioxidant compounds that safeguard cellular integrity against various forms of damage and may play a role in cancer prevention. Antioxidant compounds present in this plant facilitate the body's production of new cells and diminish the risk of colon cancer. In recent years, silver nanoparticles synthesized through green methods using ethnomedicinal herbs have been employed in cancers treatment. We have conducted an investigation into silver nanoparticles that were synthesized through green chemistry principles, utilizing the Descurainia sophia leaves extract for lung carcinoma treatment. The efficacy of Ag NPs against prevalent lung cancer cells was assessed. The green-synthesized silver nanoparticles characterization was conducted utilizing X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), ultraviolet–visible spectroscopy (UV–Vis), energy-dispersive X-ray spectroscopy (EDX), and transmission electron microscopy (TEM). The findings from morphological analyses validate the nanoparticles spherical shape, which ranges in size from 20 to 60 nm. The IC50 values were determined to be 173, 125, and 109 μg/mL for HLC-1, LC-2/ad, and PC-14 cell lines, respectively. According to recent data, Ag NPs may be a useful option to support the treatment of lung cancer. Although the current study presents encouraging findings, further investigation is necessary to gain a deeper understanding of the mechanisms of action and potential side effects of silver nanoparticles on HUVEC cells.
摘要索非拉是一种民族药用植物,含有抗氧化成分,可保护细胞完整性免受各种形式的损伤,并可能在癌症预防中发挥作用。这种植物中含有的抗氧化化合物能促进身体产生新细胞,降低患结肠癌的风险。近年来,利用民族药材通过绿色方法合成的纳米银已被用于癌症治疗。我们研究了采用绿色化学原理合成的银纳米颗粒,利用鸢尾叶提取物治疗肺癌。评估了Ag NPs对流行肺癌细胞的作用。利用x射线衍射(XRD)、场发射扫描电子显微镜(FE-SEM)、紫外可见光谱(UV-Vis)、能量色散x射线光谱(EDX)和透射电子显微镜(TEM)对绿色合成的纳米银进行了表征。形态学分析的结果证实了纳米颗粒的球形,其尺寸范围从20到60纳米。HLC-1、LC-2/ad和PC-14细胞株的IC50值分别为173、125和109 μg/mL。根据最近的数据,Ag NPs可能是支持肺癌治疗的有用选择。虽然目前的研究结果令人鼓舞,但需要进一步的研究来更深入地了解银纳米颗粒对HUVEC细胞的作用机制和潜在的副作用。
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引用次数: 0
miR-375-3p predicts the severity of endometriosis and regulates cellular progression by targeting NOX4 miR-375-3p通过靶向NOX4预测子宫内膜异位症的严重程度并调节细胞进展。
IF 2.3 3区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-02-01 DOI: 10.1016/j.mcp.2024.101999
Junmei Wang , Jianling Li , Hua Han , Changhua Wang , Taiying Shi , Xueyun Yang

Background

Due to the complex pathogenesis of endometriosis, its early screening and development prediction are still challenging problems in the clinic.

Objectives

This study evaluated the significance of miR-375-3p in endometriosis onset, progression, and recurrence, aiming to identify a novel biomarker for disease diagnosis and prognosis.

Materials and methods

The study enrolled 100 patients with endometriosis and 80 healthy females. The serum miR-375-3p levels were compared between the two groups, and its diagnostic significance and predictive value were assessed by ROC and Cox regression analyses. The effect of miR-375-3p on endometriosis cell growth and motility was evaluated by CCK8 and Transwell assays.

Results

Endometriosis patients showed a lower serum miR-375-3p level relative to healthy females, and more severe the disease condition, lower the miR-375-3p in endometrial tissues is. Reducing serum miR-375-3p could discriminate endometriosis patients sensitively and specifically. Additionally, miR-375-3p was identified as a predictor for the recurrence of endometriosis together with stage, lesion size, and the levels of related hormones. In endometriosis cells, miR-375-3p was demonstrated to target NOX4 and negatively regulated its expression. Overexpressing miR-375-3p significantly suppressed cell proliferation, migration, and invasion, which was reversed by NOX4.

Conclusion

Decreasing miR-375-3p served as a biomarker for endometriosis onset, development, and recurrence. miR-375-3p regulated endometriosis cell growth and motility via negatively modulating NOX4.
背景:由于子宫内膜异位症的发病机制复杂,其早期筛查和发展预测仍是临床上的难题:由于子宫内膜异位症的发病机制复杂,其早期筛查和发展预测仍是临床上的难题:本研究评估了miR-375-3p在子宫内膜异位症发病、进展和复发中的意义,旨在为疾病诊断和预后确定一种新的生物标志物:研究对象包括100名子宫内膜异位症患者和80名健康女性。比较两组患者的血清 miR-375-3p 水平,并通过 ROC 和 Cox 回归分析评估其诊断意义和预测价值。通过CCK8和Transwell试验评估了miR-375-3p对子宫内膜异位症细胞生长和活力的影响:结果:与健康女性相比,子宫内膜异位症患者的血清 miR-375-3p 水平较低;病情越严重,子宫内膜组织中的 miR-375-3p 水平越低。降低血清中的 miR-375-3p 可以灵敏、特异地鉴别子宫内膜异位症患者。此外,miR-375-3p 与子宫内膜异位症的分期、病灶大小和相关激素水平一起被认为是子宫内膜异位症复发的预测因子。在子宫内膜异位症细胞中,miR-375-3p 被证明靶向 NOX4 并负向调节其表达。过表达 miR-375-3p 能显著抑制细胞增殖、迁移和侵袭,而 NOX4 能逆转这种抑制作用:miR-375-3p通过负向调节NOX4来调控子宫内膜异位症细胞的生长和运动。
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引用次数: 0
miR-28–3p suppresses gastric cancer growth and EMT-driven metastasis by targeting the ARF6/Hedgehog axis miR-28-3p通过靶向ARF6/Hedgehog轴抑制胃癌生长和emt驱动的转移。
IF 2.3 3区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-02-01 DOI: 10.1016/j.mcp.2025.102010
Hua Ji , Sicheng Liu , Libo Yang , Yunhua Wu , Huanqing Zhang , Xueqing Liu , Linhai Li , Lihua Li
Gastric cancer (GC), among the most prevalent malignant tumors globally, demonstrates a rapid metastasis rate leading to high mortality. While microRNAs (miRNAs) have been recognized as critical regulators of tumor progression, the specific role of miR-28–3p in GC remains unclear. In this study, we demonstrate that miR-28–3p acts as a tumor suppressor by inhibiting GC cell proliferation and EMT-driven migration in vitro, as well as tumor growth and metastasis in vivo. Mechanistically, miR-28–3p directly targets ADP ribosylation factor 6 (ARF6), a small GTPase identified as an oncogene in GC. We reveal that ARF6 is significantly upregulated in GC and activates the GLI1/2-dependent Hedgehog signaling pathway, promoting tumor growth and EMT. Notably, ARF6 knockdown mitigates the pro-tumor effects caused by miR-28–3p deficiency, while combined ARF6 inhibition and Hedgehog pathway suppression exhibit synergistic anti-tumor effects. This study establishes the miR-28-3p-ARF6-Hedgehog signaling axis as a critical regulatory pathway in GC progression. Our findings provide novel insights into GC pathogenesis and highlight the therapeutic potential of targeting this axis for innovative treatment strategies.
胃癌(GC)是全球最常见的恶性肿瘤之一,其转移率快,死亡率高。虽然microRNAs (miRNAs)已被认为是肿瘤进展的关键调节因子,但miR-28-3p在胃癌中的具体作用尚不清楚。在本研究中,我们证明了miR-28-3p在体外通过抑制GC细胞增殖和emt驱动的迁移以及体内肿瘤生长和转移来发挥肿瘤抑制作用。在机制上,miR-28-3p直接靶向ADP核糖化因子6 (ARF6),这是一种小的GTPase,在GC中被认为是一种致癌基因。我们发现ARF6在GC中显著上调,激活gli1 /2依赖性Hedgehog信号通路,促进肿瘤生长和EMT。值得注意的是,ARF6敲低可减轻miR-28-3p缺失引起的促肿瘤作用,而ARF6抑制与Hedgehog途径抑制联合作用则具有协同抗肿瘤作用。本研究确定miR-28-3p-ARF6-Hedgehog信号轴是GC进展的关键调控途径。我们的研究结果为GC的发病机制提供了新的见解,并强调了针对这一轴的创新治疗策略的治疗潜力。
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引用次数: 0
Circulating miR-574–5p shows diagnostic and prognostic significance and regulates oxygen-glucose deprivation (OGD)-induced inflammatory activation of microglia by targeting ATP2B2 循环miR-574-5p具有诊断和预后意义,并通过靶向ATP2B2调节氧葡萄糖剥夺(OGD)诱导的小胶质细胞炎症激活。
IF 2.3 3区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-02-01 DOI: 10.1016/j.mcp.2025.102016
Xia Yin , Chunlei Zhang

Background

Early screening is critical for the prevention of ischemic stroke. miR-574–5p was considered a promising biomarker for ischemic stroke but lacks direct confirmation. This study evaluated miR-574–5p in discriminating ischemic stroke and predicting the severity and prognosis of patients, aiming to provide novel insights into the clinical prevention of ischemic stroke.

Methods

The clinical significance of miR-574–5p was evaluated in 103 ischemic stroke patients with 87 healthy individuals as control. The potential of serum miR-574–5p in the diagnosis and prognosis of ischemic stroke was assessed by ROC and logistic regression analyses. In vitro, oxygen-glucose deprivation (OGD)-induced microglia was established. The regulation of inflammation, oxidative stress, and proliferation of microglia by miR-574–5p were assessed by cell transfection. The downstream targets of miR-574–5p were predicted from public databases, and the targeting relationship was evaluated by luciferase reporter assay.

Results

Reducing serum miR-574–5p was observed in ischemic stroke patients relative to healthy individuals, which discriminated ischemic stroke patients. Serum miR-574–5p was negatively correlated with the NIHSS score of ischemic stroke patients and was identified as a risk factor for patients’ adverse prognosis. In OGD-induced microglia, overexpressing miR-574–5p could alleviate OGD-induced inflammation and oxidative stress and promote cell growth. Among predicted targets, ATP2B2 was upregulated in ischemic stroke and showed a negative correlation with miR-574–5p. miR-574–5p negatively regulated ATP2B2 in OGD-induced microglia, and the overexpression of ATP2B2 reversed the protective effect of miR-574–5p.

Conclusion

miR-574–5p acted as a biomarker for ischemic stroke and mediated neuroinflammation via targeting ATP2B2.
背景:早期筛查对预防缺血性脑卒中至关重要。miR-574-5p被认为是缺血性卒中的有希望的生物标志物,但缺乏直接证实。本研究评估miR-574-5p在判别缺血性脑卒中、预测患者严重程度和预后中的作用,旨在为缺血性脑卒中的临床预防提供新的见解。方法:评价103例缺血性脑卒中患者miR-574-5p的临床意义,87例健康人作为对照。采用ROC和logistic回归分析评估血清miR-574-5p在缺血性脑卒中诊断和预后中的潜力。体外建立氧葡萄糖剥夺(OGD)诱导的小胶质细胞。通过细胞转染评估miR-574-5p对炎症、氧化应激和小胶质细胞增殖的调节作用。从公共数据库中预测miR-574-5p的下游靶标,并通过荧光素酶报告基因检测评估其靶向关系。结果:缺血性脑卒中患者血清miR-574-5p较健康人降低,可区分缺血性脑卒中患者。血清miR-574-5p与缺血性脑卒中患者NIHSS评分呈负相关,被认为是患者预后不良的危险因素。在ogd诱导的小胶质细胞中,过表达miR-574-5p可以减轻ogd诱导的炎症和氧化应激,促进细胞生长。在预测的靶点中,ATP2B2在缺血性卒中中上调,并与miR-574-5p呈负相关。在ogd诱导的小胶质细胞中,miR-574-5p负向调节ATP2B2, ATP2B2的过表达逆转了miR-574-5p的保护作用。结论:miR-574-5p通过靶向ATP2B2作为缺血性卒中和介导的神经炎症的生物标志物。
{"title":"Circulating miR-574–5p shows diagnostic and prognostic significance and regulates oxygen-glucose deprivation (OGD)-induced inflammatory activation of microglia by targeting ATP2B2","authors":"Xia Yin ,&nbsp;Chunlei Zhang","doi":"10.1016/j.mcp.2025.102016","DOIUrl":"10.1016/j.mcp.2025.102016","url":null,"abstract":"<div><h3>Background</h3><div>Early screening is critical for the prevention of ischemic stroke. miR-574–5p was considered a promising biomarker for ischemic stroke but lacks direct confirmation. This study evaluated miR-574–5p in discriminating ischemic stroke and predicting the severity and prognosis of patients, aiming to provide novel insights into the clinical prevention of ischemic stroke.</div></div><div><h3>Methods</h3><div>The clinical significance of miR-574–5p was evaluated in 103 ischemic stroke patients with 87 healthy individuals as control. The potential of serum miR-574–5p in the diagnosis and prognosis of ischemic stroke was assessed by ROC and logistic regression analyses. In vitro, oxygen-glucose deprivation (OGD)-induced microglia was established. The regulation of inflammation, oxidative stress, and proliferation of microglia by miR-574–5p were assessed by cell transfection. The downstream targets of miR-574–5p were predicted from public databases, and the targeting relationship was evaluated by luciferase reporter assay.</div></div><div><h3>Results</h3><div>Reducing serum miR-574–5p was observed in ischemic stroke patients relative to healthy individuals, which discriminated ischemic stroke patients. Serum miR-574–5p was negatively correlated with the NIHSS score of ischemic stroke patients and was identified as a risk factor for patients’ adverse prognosis. In OGD-induced microglia, overexpressing miR-574–5p could alleviate OGD-induced inflammation and oxidative stress and promote cell growth. Among predicted targets, ATP2B2 was upregulated in ischemic stroke and showed a negative correlation with miR-574–5p. miR-574–5p negatively regulated ATP2B2 in OGD-induced microglia, and the overexpression of ATP2B2 reversed the protective effect of miR-574–5p.</div></div><div><h3>Conclusion</h3><div>miR-574–5p acted as a biomarker for ischemic stroke and mediated neuroinflammation via targeting ATP2B2.</div></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"79 ","pages":"Article 102016"},"PeriodicalIF":2.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069239","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
Serum miR-155–5p assists the diagnostic sensitivity and accuracy of low-dose spiral CT imaging in early lung cancer 血清miR-155-5p有助于早期肺癌低剂量螺旋CT成像诊断的敏感性和准确性。
IF 2.3 3区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-12-01 DOI: 10.1016/j.mcp.2024.101994
Fei Li, Wenwen Han, Hailong Sun

Background

Low-dose spiral CT imaging has been employed for cancer diagnosis, but its sensitivity and specificity were unsatisfactory. MicroRNAs have been considered an approach for screening cancers, and the function of miR-155–5p in lung cancer has been previously revealed.

Objectives

This study assessed the diagnostic value of combining low-dose spiral CT with serum miR-155–5p in lung cancer aiming to explore a novel strategy to assist the clinical cancer diagnosis.

Methods

This study enrolled 115 lung cancer patients and 115 patients with benign lung diseases as control. All patients received low-dose spiral CT imaging, and serum miR-155–5p levels were analyzed by PCR. The diagnostic potential of miR-155–5p in lung cancer was evaluated by receiver operating curve (ROC), and its significance in evaluating the risk of lung cancer was evaluated by logistic regression analysis. The consistency of serum miR-155–5p and low-dose spiral CT imaging with pathological examination was assessed by the Kappa test.

Results

Reduced serum miR-155–5p indicated the risk of lung cancer in patients with benign lung diseases. Decreased serum miR-155–5p showed significant diagnostic value in early lung cancer and was significantly associated with disease severity. Low-dose spiral CT imaging showed significant diagnostic value in early lung cancer and showed middle consistency with pathological examination. Combining low-dose spiral CT imaging with serum miR-155–5p improved the diagnostic sensitivity and accuracy in early lung cancer, reduced the false positive rate, and showed better consistency with pathological examination.

Conclusion

Serum miR-155–5p levels could assist the early detection of lung cancer by low-dose spiral CT examination.
背景:低剂量螺旋CT成像已被用于肿瘤诊断,但其敏感性和特异性不理想。microrna一直被认为是筛查癌症的一种方法,miR-155-5p在肺癌中的功能此前已被揭示。目的:本研究评估低剂量螺旋CT联合血清miR-155-5p对肺癌的诊断价值,旨在探索辅助临床癌症诊断的新策略。方法:本研究纳入115例肺癌患者和115例肺部良性疾病患者作为对照。所有患者均接受低剂量螺旋CT成像,并通过PCR分析血清miR-155-5p水平。采用受试者工作曲线(receiver operating curve, ROC)评价miR-155-5p在肺癌中的诊断潜力,采用logistic回归分析评价miR-155-5p在肺癌风险评价中的意义。采用Kappa试验评估血清miR-155-5p及低剂量螺旋CT成像与病理检查的一致性。结果:血清miR-155-5p降低提示肺部良性疾病患者发生肺癌的风险。血清miR-155-5p降低对早期肺癌具有重要的诊断价值,且与疾病严重程度显著相关。低剂量螺旋CT对早期肺癌的诊断价值显著,与病理检查的一致性中等。低剂量螺旋CT影像联合血清miR-155-5p可提高早期肺癌诊断的敏感性和准确性,降低假阳性率,与病理检查的一致性更好。结论:血清miR-155-5p水平有助于低剂量螺旋CT检查早期发现肺癌。
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引用次数: 0
LncRNA PVT1 promotes malignant progression by regulating the miR-7-5p/CDKL1 axis in oral squamous cell carcinoma LncRNA PVT1通过调节miR-7-5p/CDKL1轴在口腔鳞状细胞癌中促进恶性进展。
IF 2.3 3区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-12-01 DOI: 10.1016/j.mcp.2024.101995
Jun Li , Shuxin Ding , Min Li , Bo Zou , Miaomiao Chu , Guohao Gu , Cheng Chen , Yu-jiao Liu , Ke Zheng , Zhen Meng
Oral squamous cell carcinoma (OSCC), one of the most common types of head and neck squamous cell carcinoma (HNSCC), is characterized by high incidence and mortality. PVT1 is a long non-coding RNA (lncRNA) that plays an oncogenic role in various cancer types. This study aims to reveal the role and underlying molecular mechanism of PVT1 in OSCC progression. The expression levels of PVT1, miR-7-5p, and CDKL1 mRNA were evaluated using qRT-PCR. Western blot and IHC analysis were conducted to determine the protein expression of CDKL1. The biological functions of PVT1, miR-7-5p, and CDKL1 in OSCC were investigated through CCK-8, transwell migration and invasion assays. In vivo experiments utilized a xenograft model to examine the impact of PVT1 on OSCC. Furthermore, the interaction among PVT1, miR-7-5p, and CDKL1 was explored using RNA pull down assay and luciferase reporter assays. We found that PVT1 enhanced cell proliferation, migration, and invasion by targeting CDKL1. In addition, PVT1 functions as a sponge to modulate miR-7-5p, thereby influencing the expression of CDKL1 and the progression of OSCC. In conclusion, this study illustrates that the "PVT1/miR-7-5p/CDKL1" pathway is capable of promoting the progression of OSCC and may serve as a promising target for developing treatment strategies for OSCC.
口腔鳞状细胞癌(Oral squamous cell carcinoma, OSCC)是头颈部鳞状细胞癌(HNSCC)中最常见的类型之一,具有高发病率和高死亡率的特点。PVT1是一种长链非编码RNA (lncRNA),在多种癌症类型中发挥致癌作用。本研究旨在揭示PVT1在OSCC进展中的作用及其分子机制。采用qRT-PCR技术评估PVT1、miR-7-5p和CDKL1 mRNA的表达水平。Western blot和IHC检测CDKL1蛋白表达。通过CCK-8、跨井迁移和侵袭试验研究PVT1、miR-7-5p和CDKL1在OSCC中的生物学功能。体内实验采用异种移植模型来研究PVT1对OSCC的影响。此外,通过RNA拉下实验和荧光素酶报告基因检测,探讨了PVT1、miR-7-5p和CDKL1之间的相互作用。我们发现PVT1通过靶向CDKL1增强细胞增殖、迁移和侵袭。此外,PVT1作为海绵调节miR-7-5p,从而影响CDKL1的表达和OSCC的进展。总之,本研究表明,“PVT1/miR-7-5p/CDKL1”通路能够促进OSCC的进展,并可能作为制定OSCC治疗策略的有希望的靶点。
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引用次数: 0
Impact of GRM7 gene variations on glioblastoma risk in the Iranian population GRM7基因变异对伊朗人群胶质母细胞瘤风险的影响
IF 2.3 3区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-12-01 DOI: 10.1016/j.mcp.2024.101996
Elena Jamali , Atefeh Harsij , Mohammadamin Yarahmadi , Farahnaz Bidari-Zerehpoush , Yasaman Gholinezhad , Solat Eslami , Hossein Farahzadi , Fariba Agahi , Mohadeseh Fathi , Soudeh Ghafouri-Fard , Mohammad Samadian

Aim

The metabotropic glutamate receptor, GRM7 is a gene in the neurotransmitters prognostic signatures. Downregulation of this gene is associated with the progression of glioma tumors and has a negative impact on the immune response.

Methods

In the present study, we aim to assess the associations between rs6782011 and rs779867 SNPs within this gene and risk of glioblastoma multiforme (GBM) in Iranian population.

Results

There was a noteworthy difference in distribution of genotypes (P value = 0.001) and alleles (P value = 0.0002) of rs779867 between total GBM cases (n = 299) and total normal controls (n = 302). In addition, the significant difference in genotypes and alleles distribution was observed for both male and female GBM cases vs. respective normal controls. For rs6782011 variant, the significant difference in genotypes distribution was observed between male GBM cases (n = 187) vs. respective normal controls (n = 156) (P value = 0.004) and between total GBM cases (n = 299) vs. total normal controls (n = 302) (P value = 0.02). However, there was no significant difference in genotypes distribution between female GBM cases and respective normal controls (P value = 0.1). Distribution of rs6782011 alleles was not different between total GBM cases and normal controls; and between male GBM cases and male normal controls. However, there was a significant difference in alleles distribution between female GBM cases and female normal controls. Conclusion: Taken together, the mentioned polymorphisms might affect risk of GBM in Iranian population. Future studies are needed to elaborate the underlying mechanism.
目的:代谢性谷氨酸受体GRM7是影响神经递质预后的基因。该基因的下调与神经胶质瘤的进展有关,并对免疫反应产生负面影响。方法:在本研究中,我们旨在评估该基因内rs6782011和rs779867 snp与伊朗人群多形性胶质母细胞瘤(GBM)风险之间的关系。结果:rs779867基因型分布(P值=0.001)和等位基因分布(P值= 0.0002)在GBM总病例(n=299)和正常对照组(n=302)之间有显著差异。此外,男性和女性GBM病例的基因型和等位基因分布与正常对照有显著差异。对于rs6782011变异,男性GBM病例(n=187)与正常对照(n=156)之间的基因型分布差异显著(P值=0.004),总GBM病例(n=299)与总正常对照(n=302)之间的基因型分布差异显著(P值=0.02)。而女性GBM病例的基因型分布与正常对照无显著差异(P值= 0.1)。rs6782011等位基因在GBM总病例和正常对照间的分布无显著差异;男性GBM病例与男性正常对照之间的差异。然而,女性GBM病例的等位基因分布与女性正常对照有显著差异。结论:综上所述,上述多态性可能影响伊朗人群GBM的发病风险。未来的研究需要阐明潜在的机制。
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引用次数: 0
SQLE promotes osteosarcoma progression via activating TGFβ/SMAD signaling pathway SQLE通过激活TGFβ/SMAD信号通路促进骨肉瘤进展。
IF 2.3 3区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-12-01 DOI: 10.1016/j.mcp.2024.101993
Qi Song, Lina He, Jing Feng

Background

The prognosis of advanced osteosarcoma (OS) has remained stagnant in last decades, requiring the identification of novel therapeutic targets. Recently, much attention was paid to the role of squalene epoxidase (SQLE), a rate-limiting enzyme in cholesterol metabolism, in the field of oncology, while the specific role of SQLE in OS has not been sufficiently elucidated. The present study aims to investigate the role of SQLE in the progression of OS and explore the potential mechanisms.

Methods

The expression levels of SQLE in OS tissues and adjacent normal tissues were compared using bioinformatic methods and experiments. Kaplan-Meier survival analysis and univariate and multivariate Cox analysis were performed to detect the association of SQLE expression and patient’ prognosis. Stably cell lines with SQLE knockdown or overexpression were constructed by lentivirus infection. CCK-8, colony formation, scratch healing, and Transwell invasion assays were carried out to explore the effect of SQLE knockdown or overexpression on the proliferation, migration, and invasion of OS cells. Gene set enrichment analysis was conducted to reveal signaling pathways associated with SQLE expression. The effect of SQLE on TGFβ/SMAD signaling pathway were explored by Western blot assay.

Results

Here, we found a notable rise of SQLE expression in OS tissues and cell lines. Survival analysis showed that individuals with high SQLE expression had a lower median overall survival time compared to those with low SQLE expression. Univariate and multivariate Cox regression analyses showed that SQLE might have the potency to serve as an independently prognostic biomarker in OS. Loss- and gain-of-function experiments indicated that silence of SQLE suppressed OS cell proliferation, migration, and invasion, while overexpression of SQLE exerted the opposite effects. Mechanistically, TGF-β signaling pathway was identified as the downstream pathway of SQLE through bioinformatic methods, and the results of Western blot assay showed that SQLE positively regulated the activity of TGFβ1/SMAD2/3 signaling in OS. Resue experiments demonstrated that SB431542, a small molecule that inhibits TGFβ/SMAD signaling, could partly reverse the promoting effects of SQLE on OS cell proliferation, migration, and invasion.

Conclusion

Our results provided preliminary evidences that SQLE was a tumor-promoting factor and prognosis predictor in OS. SQLE promoted OS cell proliferation, migration, and invasion via activating TGFβ/SMAD signaling and targeting SQLE might be a potential strategy for the treatment of OS.
背景:在过去的几十年里,晚期骨肉瘤(OS)的预后一直停滞不前,需要寻找新的治疗靶点。近年来,角鲨烯环氧化酶(SQLE)作为一种限制胆固醇代谢的酶在肿瘤领域的作用受到了广泛的关注,但SQLE在OS中的具体作用尚未得到充分的阐明。本研究旨在探讨SQLE在OS进展中的作用,并探讨其可能的机制。方法:采用生物信息学方法和实验方法比较SQLE在OS组织和相邻正常组织中的表达水平。采用Kaplan-Meier生存分析、单因素和多因素Cox分析检测SQLE表达与患者预后的关系。通过慢病毒感染构建稳定的SQLE敲低或过表达细胞系。通过CCK-8、菌落形成、抓痕愈合和Transwell侵袭实验,探讨SQLE敲低或过表达对OS细胞增殖、迁移和侵袭的影响。通过基因集富集分析揭示与SQLE表达相关的信号通路。western blot检测SQLE对tgf - β/SMAD信号通路的影响。结果:我们发现SQLE在OS组织和细胞系中的表达明显升高。生存分析显示,与低SQLE表达的个体相比,高SQLE表达的个体的中位总生存时间较低。单因素和多因素Cox回归分析显示,SQLE可能有潜力作为OS的独立预后生物标志物。功能缺失和功能获得实验表明,SQLE的沉默抑制了OS细胞的增殖、迁移和侵袭,而过表达SQLE则起到相反的作用。机制上,通过生物信息学方法确定TGF-β信号通路为SQLE的下游通路,western blot检测结果显示,SQLE在OS中正调控TGF-β 1/SMAD2/3信号的活性。Resue实验表明SB431542是一种抑制TGFβ/SMAD信号的小分子,可以部分逆转SQLE对OS细胞增殖、迁移和侵袭的促进作用。结论:我们的结果为SQLE是OS的促瘤因子和预后预测因子提供了初步证据。SQLE通过激活TGFβ/SMAD信号通路促进OS细胞增殖、迁移和侵袭,靶向SQLE可能是治疗OS的一种潜在策略。
{"title":"SQLE promotes osteosarcoma progression via activating TGFβ/SMAD signaling pathway","authors":"Qi Song,&nbsp;Lina He,&nbsp;Jing Feng","doi":"10.1016/j.mcp.2024.101993","DOIUrl":"10.1016/j.mcp.2024.101993","url":null,"abstract":"<div><h3>Background</h3><div>The prognosis of advanced osteosarcoma (OS) has remained stagnant in last decades, requiring the identification of novel therapeutic targets. Recently, much attention was paid to the role of squalene epoxidase (SQLE), a rate-limiting enzyme in cholesterol metabolism, in the field of oncology, while the specific role of SQLE in OS has not been sufficiently elucidated. The present study aims to investigate the role of SQLE in the progression of OS and explore the potential mechanisms.</div></div><div><h3>Methods</h3><div>The expression levels of SQLE in OS tissues and adjacent normal tissues were compared using bioinformatic methods and experiments. Kaplan-Meier survival analysis and univariate and multivariate Cox analysis were performed to detect the association of SQLE expression and patient’ prognosis. Stably cell lines with SQLE knockdown or overexpression were constructed by lentivirus infection. CCK-8, colony formation, scratch healing, and Transwell invasion assays were carried out to explore the effect of SQLE knockdown or overexpression on the proliferation, migration, and invasion of OS cells. Gene set enrichment analysis was conducted to reveal signaling pathways associated with SQLE expression. The effect of SQLE on TGFβ/SMAD signaling pathway were explored by Western blot assay.</div></div><div><h3>Results</h3><div>Here, we found a notable rise of SQLE expression in OS tissues and cell lines. Survival analysis showed that individuals with high SQLE expression had a lower median overall survival time compared to those with low SQLE expression. Univariate and multivariate Cox regression analyses showed that SQLE might have the potency to serve as an independently prognostic biomarker in OS. Loss- and gain-of-function experiments indicated that silence of SQLE suppressed OS cell proliferation, migration, and invasion, while overexpression of SQLE exerted the opposite effects. Mechanistically, TGF-β signaling pathway was identified as the downstream pathway of SQLE through bioinformatic methods, and the results of Western blot assay showed that SQLE positively regulated the activity of TGFβ1/SMAD2/3 signaling in OS. Resue experiments demonstrated that SB431542, a small molecule that inhibits TGFβ/SMAD signaling, could partly reverse the promoting effects of SQLE on OS cell proliferation, migration, and invasion.</div></div><div><h3>Conclusion</h3><div>Our results provided preliminary evidences that SQLE was a tumor-promoting factor and prognosis predictor in OS. SQLE promoted OS cell proliferation, migration, and invasion via activating TGFβ/SMAD signaling and targeting SQLE might be a potential strategy for the treatment of OS.</div></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"78 ","pages":"Article 101993"},"PeriodicalIF":2.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142752058","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
Role of microRNAs in neutrophil extracellular trap formation and prevention: Systematic narrative review. 微RNA在中性粒细胞胞外捕获器的形成和预防中的作用:系统叙述性综述。
IF 2.3 3区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-12-01 Epub Date: 2024-10-13 DOI: 10.1016/j.mcp.2024.101986
Bashdar Mahmud Hussen, Mohammed Fatih Rasul, Goran Sedeeq Hama Faraj, Snur Rasool Abdullah, Seerwan Hamadameen Sulaiman, Hasan Pourmoshtagh, Mohammad Taheri

Active neutrophils play a variety of roles in both innate and adaptive immune responses, and one of the most vital roles is the formation and release of neutrophil extracellular traps (NETs). NETs are created when neutrophils release their chromatin contents to get and eradicate pathogenic organisms essentially. While NET helps fight bacteria, viruses, parasites, and infections, it is also linked to asthma, atherosclerosis, and cancer metastasis. Thus, understanding the molecular mechanisms behind NETosis formation and its inhibition is crucial for developing safe and effective therapies. This systematic review aims to identify the list of miRNAs that are associated with the formation of NETosis and illustrate the mechanism of action by classifying them based on their expression site. Moreover, it summarizes the list of miRNAs that can be targeted therapeutically to reduce NETosis in various disorders. The current study entailed the searching of PubMed and Google Scholar for articles related to the research topic role of miRNAs in NETosis in all types of disorders. The search terms and phrases included "NETs," "neutrophil extracellular traps," "NETosis," "miRNA," "miR," and "micro-RNA." The search was limited to articles published in English since October 2024 in both databases. Following a review of 23 papers, 19 of them met the inclusion and exclusion criteria of this study. Four papers have been removed as they are duplicated or do not meet our criteria. According to the published articles till October 2024, there are 14 miRNAs involved in the molecular pathway of NETosis which are miR-155, miR-1696, miR-7, miR-223, miR-146a, miR-142a-3p, miR-3146, miR-505, miR-4512, miR-15b-5p, miR-16-5p, miR-26b-5p, miR-125a-3p and miR-378a-3p. Moreover, eight miRNAs have been identified as possible therapeutic targets for the suppression of NETosis based on in-vivo studies carried out in various organisms, which are miR-155, miR-146a, miR-1696, miR-223, miR-142a-3p, miR-3146, miR-4512, miR-16-5p. Different miRNAs that are expressed inside or outside of neutrophils can regulate and influence NETosis. Eight miRNAs have also been identified as potential therapeutic targets, which can be utilized to inhibit the molecular pathways associated with NETosis and prevent its negative effects, such as asthma, atherosclerosis, cancer metastasis, and cancer recurrence. However, further human-based research is necessary to completely understand the role of miRNAs in the development of NETosis in humans.

活跃的中性粒细胞在先天性和适应性免疫反应中发挥着各种作用,其中最重要的作用之一就是形成和释放中性粒细胞胞外捕获物(NET)。当中性粒细胞释放其染色质内容物以获取和消灭病原体时,就会形成 NET。NET有助于抵抗细菌、病毒、寄生虫和感染,但也与哮喘、动脉粥样硬化和癌症转移有关。因此,了解 NETosis 形成及其抑制背后的分子机制对于开发安全有效的疗法至关重要。本系统综述旨在确定与 NETosis 形成相关的 miRNAs 列表,并根据其表达位点进行分类,从而说明其作用机制。此外,它还总结了可作为治疗靶点的 miRNA 列表,以减少各种疾病的 NETosis。目前的研究需要在 PubMed 和 Google Scholar 上搜索与 miRNA 在各类疾病的 NETosis 中的作用这一研究主题相关的文章。搜索关键词和短语包括 "NETs"、"嗜中性粒细胞胞外陷阱"、"NETosis"、"miRNA"、"miR "和 "micro-RNA"。检索仅限于自 2024 年 10 月以来在这两个数据库中发表的英文文章。在对 23 篇论文进行审查后,其中 19 篇符合本研究的纳入和排除标准。有四篇论文因重复或不符合我们的标准而被删除。根据截至 2024 年 10 月发表的文章,有 14 个 miRNA 参与了 NETosis 的分子通路,它们是 miR-155、miR-1696、miR-7、miR-223、miR-146a、miR-142a-3p、miR-3146、miR-505、miR-4512、miR-15b-5p、miR-16-5p、miR-26b-5p、miR-125a-3p 和 miR-378a-3p。此外,根据在不同生物体内进行的体内研究,有 8 种 miRNA 被确定为抑制 NETosis 的可能治疗靶点,它们是 miR-155、miR-146a、miR-1696、miR-223、miR-142a-3p、miR-3146、miR-4512 和 miR-16-5p。在中性粒细胞内部或外部表达的不同 miRNA 可调节和影响 NETosis。有 8 种 miRNA 被确定为潜在的治疗靶点,可用于抑制与 NETosis 相关的分子通路,防止其负面影响,如哮喘、动脉粥样硬化、癌症转移和癌症复发。然而,要完全了解 miRNA 在人类 NETosis 发展过程中的作用,还需要进一步的人体研究。
{"title":"Role of microRNAs in neutrophil extracellular trap formation and prevention: Systematic narrative review.","authors":"Bashdar Mahmud Hussen, Mohammed Fatih Rasul, Goran Sedeeq Hama Faraj, Snur Rasool Abdullah, Seerwan Hamadameen Sulaiman, Hasan Pourmoshtagh, Mohammad Taheri","doi":"10.1016/j.mcp.2024.101986","DOIUrl":"10.1016/j.mcp.2024.101986","url":null,"abstract":"<p><p>Active neutrophils play a variety of roles in both innate and adaptive immune responses, and one of the most vital roles is the formation and release of neutrophil extracellular traps (NETs). NETs are created when neutrophils release their chromatin contents to get and eradicate pathogenic organisms essentially. While NET helps fight bacteria, viruses, parasites, and infections, it is also linked to asthma, atherosclerosis, and cancer metastasis. Thus, understanding the molecular mechanisms behind NETosis formation and its inhibition is crucial for developing safe and effective therapies. This systematic review aims to identify the list of miRNAs that are associated with the formation of NETosis and illustrate the mechanism of action by classifying them based on their expression site. Moreover, it summarizes the list of miRNAs that can be targeted therapeutically to reduce NETosis in various disorders. The current study entailed the searching of PubMed and Google Scholar for articles related to the research topic role of miRNAs in NETosis in all types of disorders. The search terms and phrases included \"NETs,\" \"neutrophil extracellular traps,\" \"NETosis,\" \"miRNA,\" \"miR,\" and \"micro-RNA.\" The search was limited to articles published in English since October 2024 in both databases. Following a review of 23 papers, 19 of them met the inclusion and exclusion criteria of this study. Four papers have been removed as they are duplicated or do not meet our criteria. According to the published articles till October 2024, there are 14 miRNAs involved in the molecular pathway of NETosis which are miR-155, miR-1696, miR-7, miR-223, miR-146a, miR-142a-3p, miR-3146, miR-505, miR-4512, miR-15b-5p, miR-16-5p, miR-26b-5p, miR-125a-3p and miR-378a-3p. Moreover, eight miRNAs have been identified as possible therapeutic targets for the suppression of NETosis based on in-vivo studies carried out in various organisms, which are miR-155, miR-146a, miR-1696, miR-223, miR-142a-3p, miR-3146, miR-4512, miR-16-5p. Different miRNAs that are expressed inside or outside of neutrophils can regulate and influence NETosis. Eight miRNAs have also been identified as potential therapeutic targets, which can be utilized to inhibit the molecular pathways associated with NETosis and prevent its negative effects, such as asthma, atherosclerosis, cancer metastasis, and cancer recurrence. However, further human-based research is necessary to completely understand the role of miRNAs in the development of NETosis in humans.</p>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":" ","pages":"101986"},"PeriodicalIF":2.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142401780","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}
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Molecular and Cellular Probes
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