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Screening and identification Hub genes associated with immune cell infiltration and critical biomarkers in osteosarcoma 筛选和鉴定骨肉瘤中与免疫细胞浸润相关的中枢基因和关键生物标志物。
IF 2.3 3区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-05-13 DOI: 10.1016/j.mcp.2025.102031
Xin Song , Sihao Chen , Junning Cheng , Haiyu Li , Ruixin Wu , Min Yan , Min Wang , Jie Li , Aishun Jin , Wang Wang

Purpose

Osteosarcoma (OS) exhibits limited immune cell infiltration that directly contributes to poor prognosis. This study sought to screen and identify pivotal biomarkers of OS immune infiltration and early diagnosis of OS.

Methods

The immune cell infiltration profiles with transcriptome sequencing data from 88 OS samples were explored with CIBERSORT algorithm. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Protein-protein interaction (PPI) network analyses were applied to identify hub genes, with the expressions confirmed by dual immunofluorescence in 50 OS samples. The new biomarker gene HTRA1 were examined by immunohistochemistry and validated by the Immune score and immune gene expression profile analyses. The impact of HTRA1 on OS prognosis was verified by Least absolute shrinkage and selection operator (LASSO) regression analysis. The biological effect of HTRA1 was characterized in MG63 cells.

Result

CD8+ T cells, activated memory CD4+ T cells and plasma cells were positively correlated with the prognosis of OS. Hub genes CCL5, CXCL9, CXCL13, and HTRA1, exhibited positive correlation with the infiltration of both CD8+ T cells and CD4+ T cells. HTRA1 expression was reduced in osteosarcoma tissues, which was positively correlated with immune scores and the expressions of immune-related genes. High levels of HTRA1 were associated with favorable OS prognosis, and could negatively impacted MG63 malignant characteristics.

Conclusion

CCL5, CXCL9, CXCL13, and HTRA1 were OS hub genes positively correlate with CD8+ T cell and CD4+ T cell infiltrations. HTRA1 can serve as an underlying biomarker for the prognosis and immunotherapy of OS.
目的:骨肉瘤(OS)表现出有限的免疫细胞浸润,直接导致预后不良。本研究旨在筛选和鉴定OS免疫浸润和OS早期诊断的关键生物标志物。方法:采用CIBERSORT算法对88例OS样本的免疫细胞浸润谱进行转录组测序分析。应用基因本体(GO)、京都基因与基因组百科全书(KEGG)和蛋白-蛋白相互作用(PPI)网络分析方法鉴定中心基因,并通过双免疫荧光法对50份OS样本的表达进行确认。通过免疫组织化学检测新的生物标志物基因HTRA1,并通过免疫评分和免疫基因表达谱分析进行验证。采用最小绝对收缩和选择算子(LASSO)回归分析验证HTRA1对OS预后的影响。在MG63细胞中表征了HTRA1的生物学效应。结果:CD8+ T细胞、活化记忆CD4+ T细胞、浆细胞与OS预后呈正相关。枢纽基因CCL5、CXCL9、CXCL13和HTRA1与CD8+ T细胞和CD4+ T细胞浸润均呈正相关。骨肉瘤组织中HTRA1表达降低,与免疫评分及免疫相关基因表达呈正相关。高水平的HTRA1与良好的OS预后相关,并可能对MG63的恶性特征产生负面影响。结论:CCL5、CXCL9、CXCL13和HTRA1是OS中心基因,与CD8+ T细胞和CD4+ T细胞浸润呈正相关。HTRA1可以作为OS预后和免疫治疗的潜在生物标志物。
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引用次数: 0
ANP32E expression in pancreatic cancer is associated with impaired gemcitabine efficacy and poor patient prognosis 胰腺癌中ANP32E表达与吉西他滨疗效受损和患者预后不良相关
IF 2.3 3区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-04-28 DOI: 10.1016/j.mcp.2025.102030
Xiaohong Liu , Yelin Zhao , Li Zhang , Junting Wang , Liaoxin Luo , Shihui Zhang , Qin Zhu , Yuchen Shi , Chenyu Yuan , Qifeng Xiao , Mengran Xiong , Yuanyuan Duan , Hebing Chen , Hongjuan Yao , Lin Cai , Jianwei Zhang , Guangxi Li , Liang Li

Purpose

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive and fatal malignancy, although gemcitabine is administered as a single or combined therapeutic agent. Our previous study demonstrated that ANP32E overexpression promoted PDAC cell proliferation. However, whether it affects treatment outcome and clinical prognosis is still unclear. In the present study, we aimed to determine whether ANP32E is negatively associated with the treatment outcome of gemcitabine.

Methods

We collected clinical characteristics and treatment information from a total of 75 PDAC patients to assess the association of ANP32E expression via immunohistochemical (IHC) staining with overall survival (OS) in patients who were or were not treated with gemcitabine-based chemotherapy, followed by a clinical replication study with transcriptomic data from the TCGA database and functional validation experiments involving the knockdown of ANP32E in the Hup-T3 and SU86.86 human pancreatic cancer cell lines.

Results

We demonstrated the interference effect of ANP32E on gemcitabine efficacy and patient prognosis in PDAC patients by using our own clinical samples or publicly available TCGA datasets. Downregulation of ANP32E significantly sensitized Hup-T3 and SU86.86 cells to gemcitabine, which was consistent with the results of the above association studies.

Conclusion

Our findings suggest that ANP32E might serve as a negative biomarker for poor prognosis and a predictive indicator for poor gemcitabine efficacy. These findings suggest that ANP32E might be a potential therapeutic target to help develop effective drugs to overcome gemcitabine resistance and reduce the risk for relapse or metastasis in patients with PDAC.
目的:胰腺导管腺癌(PDAC)是一种高度侵袭性和致命性的恶性肿瘤,尽管吉西他滨是单一或联合治疗药物。我们之前的研究表明ANP32E过表达促进了PDAC细胞的增殖。然而,是否影响治疗结果和临床预后尚不清楚。在本研究中,我们旨在确定ANP32E是否与吉西他滨治疗结果负相关。方法收集75例PDAC患者的临床特征和治疗信息,通过免疫组化(IHC)染色评估ANP32E表达与接受或未接受吉西他滨化疗的患者总生存期(OS)的关系。随后,利用TCGA数据库的转录组学数据进行了临床复制研究,并在Hup-T3和SU86.86人胰腺癌细胞系中进行了ANP32E敲低的功能验证实验。结果我们通过自己的临床样本或公开的TCGA数据集证明了ANP32E对吉西他滨疗效和PDAC患者预后的干扰作用。ANP32E的下调使Hup-T3和SU86.86细胞对吉西他滨显着增敏,这与上述关联研究的结果一致。结论ANP32E可能是不良预后的阴性生物标志物,也是吉西他滨疗效差的预测指标。这些发现表明,ANP32E可能是一个潜在的治疗靶点,有助于开发有效的药物来克服吉西他滨耐药,降低PDAC患者复发或转移的风险。
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引用次数: 0
The clinicopathologic and prognostic value of CD44 expression in patients with non-small cell lung cancer: A systematic review and meta-analysis 非小细胞肺癌患者CD44表达的临床病理和预后价值:一项系统综述和荟萃分析
IF 2.3 3区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-03-24 DOI: 10.1016/j.mcp.2025.102028
Elmira Alaei , Najma Farahani , Sima Orouei , Mina Alimohammadi , Salman Daneshi , Tahoora Mousavi , Behnaz Mahmoodieh , Afshin Taheriazam , Payman Rahimzadeh , Mehrdad Hashemi

Background

CD44 is a promising target in the prognosis and treatment of non-small cell lung cancer (NSCLC). The study deals with systematic review and meta-analysis to determine the association between CD44 overexpression and survival and clinicopathological characteristics in NSCLC patients.

Methods

We used the databases Google Scholar, Web of Science, PubMed, Scopus, EMBASE, and Cochrane to conduct a systematic search of English-language literature published up to September 2023. The eligible studies were retrieved on CD44 expression, clinicopathological characteristics in NSCLC patients, and reported survival rates. The Cochran's and Higgins I2 tests were used to measure heterogeneity across the included studies. P < 0.05 was considered statistically significant in all cases. The sources of heterogeneity across the included studies were identified using subgroup analysis on histology (SCC, ADC, and LCC), tumor differentiation (well, moderate, and poor), TMN stage (I/II/III/IV), OS, and lymph node metastasis (negative and positive). All statistical analyses were carried out using meta-analysis (CMA) software.

Results

The final analysis for prognostic significance and clinicopathological features on 3681 participants from 25 eligible studies. The pooled event rate of overexpression CD44 for overall survival in NSCLC was 38 % and was related to SCC with 76.6 %. Furthermore, subgroup analysis revealed a link between CD44 overexpression and moderate tumor differentiation (41.8 %). There was a substantial difference in CD44 overexpression in males, with 69.3 % (95 % CI: 64.3–73.9 %, I2 = 88.25 %) versus 31.5 % (95 % CI: 26.7–36.8 %, I2 = 92.15 %) in females. However, no significant relationship was observed between CD44 overexpression and TMN stages/lymph node metastasis.

Conclusion

The meta-analysis demonstrated that CD44 is an effective prognostic factor for NSCLC. Overexpression of CD44 has been linked to moderate tumor differentiation, SCC tumor histology, and a worse survival rate. However, no substantial relationship was found between CD44 and metastasis or TMN stages. Large-scale prospective research is required to validate CD44's clinical value as an unbiased prognostic indicator.
cd44在非小细胞肺癌(NSCLC)的预后和治疗中是一个有希望的靶点。本研究通过系统回顾和荟萃分析来确定CD44过表达与NSCLC患者生存和临床病理特征之间的关系。方法采用谷歌Scholar、Web of Science、PubMed、Scopus、EMBASE、Cochrane等数据库,系统检索截至2023年9月发表的英文文献。符合条件的研究检索了CD44表达、非小细胞肺癌患者的临床病理特征和报告的生存率。采用Cochran's和Higgins I2检验来衡量纳入研究的异质性。P & lt;0.05被认为在所有病例中具有统计学意义。通过对组织学(SCC、ADC和LCC)、肿瘤分化(好、中等和差)、TMN分期(I/II/III/IV)、OS和淋巴结转移(阴性和阳性)的亚组分析,确定了纳入研究的异质性来源。所有统计分析均采用meta分析(CMA)软件进行。结果对25项符合条件的研究中3681名受试者的预后意义和临床病理特征进行了最终分析。在非小细胞肺癌中,CD44过表达的总生存率为38%,与SCC相关的总生存率为76.6%。此外,亚组分析显示CD44过表达与中度肿瘤分化之间存在联系(41.8%)。CD44过表达在男性中有显著差异,女性为69.3% (95% CI: 64.3 - 73.9%, I2 = 88.25%),女性为31.5% (95% CI: 26.7 - 36.8%, I2 = 92.15%)。然而,CD44过表达与TMN分期/淋巴结转移之间没有显著关系。结论荟萃分析表明,CD44是非小细胞肺癌的有效预后因子。CD44的过表达与中度肿瘤分化、SCC肿瘤组织学和较差的生存率有关。然而,CD44与转移或TMN分期之间没有实质性的关系。需要大规模的前瞻性研究来验证CD44作为一种公正的预后指标的临床价值。
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引用次数: 0
Differential gene expression in uterine endometrioid cancer cells and adjusted normal tissue 子宫内膜样癌细胞与调节后正常组织的差异基因表达。
IF 2.3 3区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-03-14 DOI: 10.1016/j.mcp.2025.102027
Dominik Kodada , Dominik Hadžega , Patrik Krumpolec , Nikola Janoštiaková , Gabriela Bľandová , Pavol Janega , Zuzana Ballová , Erik Dosedla , Gabriel Minárik , Vanda Repiská
Endometrial cancer is a significant public health concern with rising incidence rates globally. Understanding the molecular mechanisms underlying this disease is crucial for developing effective therapeutic strategies. Our study aimed to characterize transcriptional changes in endometrial cancer tissues compared to adjusted healthy tissue. Using RNA sequencing, we identified 2483 differentially expressed genes (DEGs), including protein-coding genes, long non-coding RNAs (lncRNAs), and microRNAs (miRNAs). Notably, several known cancer-related genes were differentially expressed, such as MYC, AKT3, CCND1, and CDKN2A. Pathway analysis revealed significant alterations in cell cycle regulation, several signaling pathways, and metabolic processes. These findings provide valuable insights into the molecular pathways dysregulated in endometrial cancer. Our results may contribute to the development of novel therapeutic targets and biomarkers for this disease.
子宫内膜癌是一个重大的公共卫生问题,全球发病率不断上升。了解这种疾病的分子机制对于制定有效的治疗策略至关重要。我们的研究旨在描述子宫内膜癌组织与调整后的健康组织相比的转录变化特征。通过 RNA 测序,我们发现了 2483 个差异表达基因(DEGs),包括蛋白编码基因、长非编码 RNAs(lncRNAs)和 microRNAs(miRNAs)。值得注意的是,一些已知的癌症相关基因出现了差异表达,如 MYC、AKT3、CCND1 和 CDKN2A。通路分析表明,细胞周期调控、几种信号通路和代谢过程都发生了重大改变。这些发现为了解子宫内膜癌中失调的分子通路提供了有价值的见解。我们的研究结果可能有助于开发该疾病的新型治疗靶点和生物标记物。
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引用次数: 0
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 : 2025-03-14 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
BUB1-deficiency suppresses kidney renal clear cell carcinoma progression via the PI3K/Akt pathway: A bioinformatics-oriented validating study bub1缺乏通过PI3K/Akt通路抑制肾透明细胞癌进展:一项生物信息学导向的验证研究
IF 2.3 3区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-03-11 DOI: 10.1016/j.mcp.2025.102024
Xiaolin Zi , Jinpeng Ma , Xiaoxia Li , Honglei Wang , Yuchen Bao , Tao Deng , Xueli Yuan
Although great advances have been reached in the diagnosis, treatment and prognosis of kidney renal clear cell carcinoma (KIRC), the advancement of therapeutic strategies for KIRC in clinical practices have been seriously limited due to its unknown molecular mechanisms. To resolve this issue, through analyzing the datasets from the online UCSC database, a novel BUB1 gene was found to be elevated in the cancerous tissues compared to their normal tissues of KIRC, and and KIRC patients with high-expressed BUB1 tended to have a worse prognosis. The subsequent experiments validated that BUB1 protein was located in both nucleus and cytoplasm of KIRC cells, and the expression levels of BUB1 gene were significantly elevated in KIRC tissues and cells, in contrast to their normal counterparts. Loss-of-function experiments verified that knockdown of BUB1 suppressed cell proliferation, mobility, epithelial-mesenchymal transition (EMT) and tumor growth, whereas induced apoptotic cell death in the KIRC cells in vitro and in vivo. In addition, bioinformatics analysis predicted that the differentially-expressed genes (DEGs) in the BUB1-deficient cohorts were enriched in the cell division-related PI3K/Akt signal pathway, and we evidenced that silencing of BUB1 was capable of inactivating the downstream PI3K/Akt signal pathway. Of note, deficiency of BUB1-induced suppressing effects on the malignant phenotypes in KIRC cells were all reversed by co-treating cells with PI3K/Akt pathway activator 740Y-P. Furthermore, it was found that the expression status of BUB1 gene were related with epigenetic modifications, immune infiltration and immunotherapy responses in KIRC. Collectively, silencing of BUB1 inhibited the progression of KIRC through inactivating the downstream PI3K/Akt signal pathway, and BUB1 gene could be potentially used as biomarkers for the diagnosis and treatment of KIRC in clinic.
尽管肾透明细胞癌(KIRC)在诊断、治疗和预后方面取得了很大进展,但由于其分子机制尚不清楚,严重限制了临床治疗策略的进展。为了解决这一问题,通过分析在线UCSC数据库的数据集,我们发现一种新的BUB1基因在癌组织中比KIRC的正常组织中升高,并且高表达BUB1的KIRC患者往往预后更差。随后的实验证实,BUB1蛋白位于KIRC细胞的细胞核和细胞质中,并且与正常组织细胞相比,在KIRC组织细胞中,BUB1基因的表达水平显著升高。功能缺失实验证实,在体外和体内实验中,敲低BUB1可抑制细胞增殖、移动性、上皮-间质转化(epithelial-mesenchymal transition, EMT)和肿瘤生长,而诱导凋亡细胞死亡。此外,生物信息学分析预测,在BUB1缺陷队列中,差异表达基因(DEGs)在细胞分裂相关的PI3K/Akt信号通路中富集,我们证明了沉默BUB1能够使下游PI3K/Akt信号通路失活。值得注意的是,通过与PI3K/Akt通路激活剂740Y-P共处理细胞,缺乏bub1诱导的对KIRC细胞恶性表型的抑制作用全部被逆转。此外,我们还发现BUB1基因在KIRC中的表达状态与表观遗传修饰、免疫浸润和免疫治疗应答有关。综上所述,沉默BUB1基因可通过失活下游PI3K/Akt信号通路抑制KIRC的进展,并且BUB1基因有可能作为临床诊断和治疗KIRC的生物标志物。
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引用次数: 0
Down-regulated circ_0001853 inhibits lipopolysaccharide-induced endometritis progression via sponging miR-34c-5p 下调的circ_0001853通过海绵miR-34c-5p抑制脂多糖诱导的子宫内膜炎进展。
IF 2.3 3区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-03-07 DOI: 10.1016/j.mcp.2025.102023
Qian Xu, Ailing Peng, Liyun Zhao, Li Wang

Background

To investigate the diagnostic value and mechanism of action of circular RNA (circ_) circ_0001853 and microRNA (miR) miR-34c-5p in patients with endometritis.

Methods

189 patients with endometritis and 176 healthy individuals were included in this study. Venous blood serum was collected from the study subjects and stored temporarily at −80 °C. Real-time quantitative chain polymerase reaction (RT-qPCR) was used to detect circ_0001853 and miR-34c-5p expression, and receiver operating characteristic (ROC) curves assessed the diagnostic value of both in predicting endometritis. Cell counting kit (CCK8) observed cell proliferation, flow cytometry recorded apoptosis, enzyme linked immunosorbent assay (ELISA) monitored inflammatory factor expression, and dual luciferase reporter assay and RNA immunoprecipitation (RIP) verified the relationship between circ_0001853 and miR-34c-5p targeting interactions.

Results

High levels of circ_0001853 and low levels of miR-34c-5p were present in endometritis patients, and they were negatively correlated. Both circ_0001853 and miR-34c-5p alone or in combination had diagnostic value in predicting the progression of endometritis. Transfection of si-circ_0001853 promoted cell proliferation and reduced apoptosis and cellular inflammation levels induced by lipopolysaccharide (LPS) stimulation. There was a direct reciprocal targeting relationship between miR-34c-5p and circ_0001853, and the use of miR-34c-5p inhibitor resisted silencing circ_0001853 promoted cell proliferation and increased the number of apoptotic cells and cellular inflammation levels.

Conclusions

circ_0001853 is involved in endometritis progression through miR-34c-5p, i.e., low circ_0001853 promotes miR-34c-5p-induced proliferation of epithelial cells, reduces apoptosis, and suppresses inflammation levels, preventing disease progression.
背景:探讨环状RNA (circ_) circ_0001853和microRNA (miR) miR-34c-5p在子宫内膜炎患者中的诊断价值及作用机制。方法:189例子宫内膜炎患者和176名健康人作为研究对象。采集研究对象静脉血血清,在-80°C临时保存。采用实时定量链聚合酶反应(RT-qPCR)检测circ_0001853和miR-34c-5p的表达,并用受试者工作特征(ROC)曲线评估两者在预测子宫内膜炎中的诊断价值。细胞计数试剂盒(CCK8)观察细胞增殖,流式细胞术记录细胞凋亡,酶联免疫吸附试验(ELISA)监测炎症因子表达,双荧光素酶报告基因法和RNA免疫沉淀(RIP)验证circ_0001853与miR-34c-5p靶向相互作用之间的关系。结果:子宫内膜炎患者存在高水平的circ_0001853和低水平的miR-34c-5p,两者呈负相关。circ_0001853和miR-34c-5p单独或联合使用对预测子宫内膜炎的进展具有诊断价值。转染si-circ_0001853可促进细胞增殖,减少脂多糖(LPS)刺激引起的细胞凋亡和细胞炎症水平。miR-34c-5p与circ_0001853之间存在直接的相互靶向关系,使用miR-34c-5p抑制剂抵抗circ_0001853的沉默,促进细胞增殖,增加凋亡细胞数量和细胞炎症水平。结论:circ_0001853通过miR-34c-5p参与子宫内膜炎的进展,即低circ_0001853促进miR-34c-5p诱导的上皮细胞增殖,减少凋亡,抑制炎症水平,防止疾病进展。
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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 : 2025-03-07 DOI: 10.1016/j.mcp.2025.102021
Shaosheng Lou , Wang Yang , Qian Zhao , Yunshan Ouyang , Lingling Cao , Chen Lin
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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 : 2025-03-04 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
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 : 2025-03-01 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":"2025-03-01","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
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Molecular and Cellular Probes
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