Objective:Aloin,the main active component in Aloe vera(L.)Burm.f.,has shown promising anti-tumor effects.This study investigated the impact of aloin in lung squamous cell carcinoma(LUSC)and explored its functional mec...Objective:Aloin,the main active component in Aloe vera(L.)Burm.f.,has shown promising anti-tumor effects.This study investigated the impact of aloin in lung squamous cell carcinoma(LUSC)and explored its functional mechanism.Methods:We analyzed the viability,migration,invasion,proliferation,and apoptosis of two LUSC cell lines after treatment with aloin.Target molecules of aloin and downstream target transcripts of nuclear receptor subfamily 3 group C member 2(NR3C2)were predicted by bioinformatics.The biological functions of NR3C2 and metallothionein 1M(MT1M)in the malignant properties of LUSC cells were determined.A co-culture system of LUSC cells with monocyte-derived macrophages was constructed.Mouse xenograft tumor models were generated to analyze the functions of aloin and NR3C2 in the tumorigenic activity of LUSC cells and macrophage polarization in vivo.Results:Aloin suppressed malignant properties of LUSC cells in vitro.However,these effects were negated by the silencing of NR3C2.NR3C2 was found to activate MT1M transcription by binding to its promoter.Additional upregulation of MT1M suppressed the malignant behavior of LUSC cells augmented by NR3C2 silencing.Analysis of the M1 and M2 markers/cytokines in the macrophages or the culture supernatant revealed that aloin treatment or MT1M overexpression in LUSC cells enhanced M1 polarization while suppressing M2 polarization of macrophages,whereas NR3C2 silencing led to reverse trends.Consistent findings were reproduced in vivo.Conclusion:This study demonstrated that aloin activates the NR3C2/MT1M axis to suppress the malignant behavior of LUSC cells and M2 macrophage polarization.Please cite this article as:Chen YN,Lu JY,Gao CF,Fang ZR,Zhou Y.Aloin blocks the malignant behavior of lung squamous cell carcinoma cells and M2 macrophage polarization by modulating the NR3C2/MT1M axis.展开更多
Background:Non‐small cell lung cancer(NSCLC),including the lung squamous cell carcinoma(LUSC)and lung adenocarcinoma(LUAD)subtypes,is a malignant tumor type with a poor 5‐year survival rate.The identification of new...Background:Non‐small cell lung cancer(NSCLC),including the lung squamous cell carcinoma(LUSC)and lung adenocarcinoma(LUAD)subtypes,is a malignant tumor type with a poor 5‐year survival rate.The identification of new powerful diagnostic biomarkers,prognostic biomarkers,and potential therapeutic targets in NSCLC is urgently required.Methods:The UCSC Xena,UALCAN,and GEO databases were used to screen and analyze differentially expressed genes,regulatory modes,and genetic/epigenetic alterations in NSCLC.The UCSC Xena database,GEO database,tissue microarray,and immunohistochemistry staining analyses were used to evaluate the diagnostic and prognostic values.Gain‐of‐function assays were performed to examine the roles.The ESTIMATE,TIMER,Linked Omics,STRING,and DAVID algorithms were used to analyze potential molecular mechanisms.Results:NR3C2 was identified as a potentially important molecule in NSCLC.NR3C2 is expressed at low levels in NSCLC,LUAD,and LUSC tissues,which is significantly related to the clinical indexes of these patients.Receiver operating characteristic curve analysis suggests that the altered NR3C2 expression patterns have diagnostic value in NSCLC,LUAD,and especially LUSC patients.Decreased NR3C2 expression levels can help predict poor prognosis in NSCLC and LUAD patients but not in LUSC patients.These results have been confirmed both with database analysis and real‐world clinical samples on a tissue microarray.Copy number variation contributes to low NR3C2 expression levels in NSCLC and LUAD,while promoter DNA methylation is involved in its downregulation in LUSC.Two NR3C2 promoter methylation sites have high sensitivity and specificity for LUSC diagnosis with clinical application potential.NR3C2 may be a key participant in NSCLC development and progression and is closely associated with the tumor microenvironment and immune cell infiltration.NR3C2 co‐expressed genes are involved in many cancer‐related signaling pathways,further supporting a potentially significant role of NR3C2 in NSCLC.Conclusions:NR3C2 is a novel potential diagnostic and prognostic biomarker and therapeutic target in NSCLC.展开更多
目的通过网络药理学和生物信息学手段,研究益肾疏肝理气方在乳腺浸润癌(IBC)中的潜在治疗机制及关键靶点。方法首先通过TCGA(The Cancer Genome Atlas)数据库筛选IBC癌症和癌旁组织的差异表达基因并进行预后相关基因分析。通过蛋白质-...目的通过网络药理学和生物信息学手段,研究益肾疏肝理气方在乳腺浸润癌(IBC)中的潜在治疗机制及关键靶点。方法首先通过TCGA(The Cancer Genome Atlas)数据库筛选IBC癌症和癌旁组织的差异表达基因并进行预后相关基因分析。通过蛋白质-蛋白质相互作用网络(PPI)分析筛选核心(Hub)基因,并通过Coremine、TCMSP等数据库对益肾疏肝理气方的活性成分进行筛选及靶向基因预测。然后,结合筛选结果,分析相关基因在IBC中的表达差异及其与免疫细胞浸润的相关性。最后,采用分子对接技术分析NR3C2与益肾疏肝理气方中的主成分茯苓的相互作用。结果识别出490个差异表达的基因,并通过PPI网络分析筛选出多个潜在的Hub基因。通过网络药理学分析,茯苓作为益肾疏肝理气方中的核心成分,其相关活性小分子对IBC具有潜在的靶向作用。进一步的研究显示,NR3C2在IBC组织中显著下调,并与免疫细胞的浸润密切相关。NR3C2的高表达与更好的预后相关(P<0.05)。分子对接结果表明,NR3C2与茯苓中的7种小分子具有良好的结合能力。结论NR3C2可能作为IBC治疗的新靶点,其与茯苓的主要成分具有潜在的靶向关系,为益肾疏肝理气方在IBC治疗中的应用提供了理论依据。此外,NR3C2的免疫调节作用也为乳腺癌免疫治疗提供了新的研究方向。展开更多
From an evolutionary point of view, reproduction timing is an important adaptation which enables the transfer of genetic properties, thus enabling species continuation. Rodents inhabiting arid environments need reliab...From an evolutionary point of view, reproduction timing is an important adaptation which enables the transfer of genetic properties, thus enabling species continuation. Rodents inhabiting arid environments need reliable cues for triggering their reproduction. Results of previous studies showed that increased dietary salinity plays an important role as an ultimate regulator for desert adapted rodents＇ reproductive system. The authors aimed discovering pathways by which high salinity can affect the reproductive system and metabolic status of desert adapted common spiny mice, Acomys cahirinus. Mice were challenged with osmotic stress, water source salinity increased gradually from 0.9% - 5% NaCI under short days （SD） and long days （LD）. The authors assessed leptin and free fatty acid （FFA） levels using ELISA while, SYBR green technology was used for relative receptor expression （RQ） of target genes. Results revealed that serum levels of the hormone leptin were significantly （P 〈 0.05） reduced in salinity treated （ST） mice. Levels of FFA were significantly （P 〈 0.05） increased in LD- and SD-ST-males. In ST-SD females a significant increase （P 〈 0.05） in expression levels of leptin （Ob-Rt） mRNA receptor gene, in ovaries was noted. Aldosteron （Nr3c2） and vasopressin （AVP） mRNA receptor expression genes levels were significantly （P 〈 0.05） increased in both LD- and SD- ST- males.展开更多
基金Financial support was provided by the Research Start-up Funding of Changzhou University(No.ZMF19020381)。
文摘Objective:Aloin,the main active component in Aloe vera(L.)Burm.f.,has shown promising anti-tumor effects.This study investigated the impact of aloin in lung squamous cell carcinoma(LUSC)and explored its functional mechanism.Methods:We analyzed the viability,migration,invasion,proliferation,and apoptosis of two LUSC cell lines after treatment with aloin.Target molecules of aloin and downstream target transcripts of nuclear receptor subfamily 3 group C member 2(NR3C2)were predicted by bioinformatics.The biological functions of NR3C2 and metallothionein 1M(MT1M)in the malignant properties of LUSC cells were determined.A co-culture system of LUSC cells with monocyte-derived macrophages was constructed.Mouse xenograft tumor models were generated to analyze the functions of aloin and NR3C2 in the tumorigenic activity of LUSC cells and macrophage polarization in vivo.Results:Aloin suppressed malignant properties of LUSC cells in vitro.However,these effects were negated by the silencing of NR3C2.NR3C2 was found to activate MT1M transcription by binding to its promoter.Additional upregulation of MT1M suppressed the malignant behavior of LUSC cells augmented by NR3C2 silencing.Analysis of the M1 and M2 markers/cytokines in the macrophages or the culture supernatant revealed that aloin treatment or MT1M overexpression in LUSC cells enhanced M1 polarization while suppressing M2 polarization of macrophages,whereas NR3C2 silencing led to reverse trends.Consistent findings were reproduced in vivo.Conclusion:This study demonstrated that aloin activates the NR3C2/MT1M axis to suppress the malignant behavior of LUSC cells and M2 macrophage polarization.Please cite this article as:Chen YN,Lu JY,Gao CF,Fang ZR,Zhou Y.Aloin blocks the malignant behavior of lung squamous cell carcinoma cells and M2 macrophage polarization by modulating the NR3C2/MT1M axis.
基金Natural Science Foundation of Chongqing Municipality,Grant/Award Number:cstc2020jcyjmsxmX0565National Natural Science Foundation of China,Grant/Award Number:82073137Natural Science Foundation of Jilin Province,Grant/Award Number:20200201353JC。
文摘Background:Non‐small cell lung cancer(NSCLC),including the lung squamous cell carcinoma(LUSC)and lung adenocarcinoma(LUAD)subtypes,is a malignant tumor type with a poor 5‐year survival rate.The identification of new powerful diagnostic biomarkers,prognostic biomarkers,and potential therapeutic targets in NSCLC is urgently required.Methods:The UCSC Xena,UALCAN,and GEO databases were used to screen and analyze differentially expressed genes,regulatory modes,and genetic/epigenetic alterations in NSCLC.The UCSC Xena database,GEO database,tissue microarray,and immunohistochemistry staining analyses were used to evaluate the diagnostic and prognostic values.Gain‐of‐function assays were performed to examine the roles.The ESTIMATE,TIMER,Linked Omics,STRING,and DAVID algorithms were used to analyze potential molecular mechanisms.Results:NR3C2 was identified as a potentially important molecule in NSCLC.NR3C2 is expressed at low levels in NSCLC,LUAD,and LUSC tissues,which is significantly related to the clinical indexes of these patients.Receiver operating characteristic curve analysis suggests that the altered NR3C2 expression patterns have diagnostic value in NSCLC,LUAD,and especially LUSC patients.Decreased NR3C2 expression levels can help predict poor prognosis in NSCLC and LUAD patients but not in LUSC patients.These results have been confirmed both with database analysis and real‐world clinical samples on a tissue microarray.Copy number variation contributes to low NR3C2 expression levels in NSCLC and LUAD,while promoter DNA methylation is involved in its downregulation in LUSC.Two NR3C2 promoter methylation sites have high sensitivity and specificity for LUSC diagnosis with clinical application potential.NR3C2 may be a key participant in NSCLC development and progression and is closely associated with the tumor microenvironment and immune cell infiltration.NR3C2 co‐expressed genes are involved in many cancer‐related signaling pathways,further supporting a potentially significant role of NR3C2 in NSCLC.Conclusions:NR3C2 is a novel potential diagnostic and prognostic biomarker and therapeutic target in NSCLC.
文摘目的通过网络药理学和生物信息学手段,研究益肾疏肝理气方在乳腺浸润癌(IBC)中的潜在治疗机制及关键靶点。方法首先通过TCGA(The Cancer Genome Atlas)数据库筛选IBC癌症和癌旁组织的差异表达基因并进行预后相关基因分析。通过蛋白质-蛋白质相互作用网络(PPI)分析筛选核心(Hub)基因,并通过Coremine、TCMSP等数据库对益肾疏肝理气方的活性成分进行筛选及靶向基因预测。然后,结合筛选结果,分析相关基因在IBC中的表达差异及其与免疫细胞浸润的相关性。最后,采用分子对接技术分析NR3C2与益肾疏肝理气方中的主成分茯苓的相互作用。结果识别出490个差异表达的基因,并通过PPI网络分析筛选出多个潜在的Hub基因。通过网络药理学分析,茯苓作为益肾疏肝理气方中的核心成分,其相关活性小分子对IBC具有潜在的靶向作用。进一步的研究显示,NR3C2在IBC组织中显著下调,并与免疫细胞的浸润密切相关。NR3C2的高表达与更好的预后相关(P<0.05)。分子对接结果表明,NR3C2与茯苓中的7种小分子具有良好的结合能力。结论NR3C2可能作为IBC治疗的新靶点,其与茯苓的主要成分具有潜在的靶向关系,为益肾疏肝理气方在IBC治疗中的应用提供了理论依据。此外,NR3C2的免疫调节作用也为乳腺癌免疫治疗提供了新的研究方向。
文摘From an evolutionary point of view, reproduction timing is an important adaptation which enables the transfer of genetic properties, thus enabling species continuation. Rodents inhabiting arid environments need reliable cues for triggering their reproduction. Results of previous studies showed that increased dietary salinity plays an important role as an ultimate regulator for desert adapted rodents＇ reproductive system. The authors aimed discovering pathways by which high salinity can affect the reproductive system and metabolic status of desert adapted common spiny mice, Acomys cahirinus. Mice were challenged with osmotic stress, water source salinity increased gradually from 0.9% - 5% NaCI under short days （SD） and long days （LD）. The authors assessed leptin and free fatty acid （FFA） levels using ELISA while, SYBR green technology was used for relative receptor expression （RQ） of target genes. Results revealed that serum levels of the hormone leptin were significantly （P 〈 0.05） reduced in salinity treated （ST） mice. Levels of FFA were significantly （P 〈 0.05） increased in LD- and SD-ST-males. In ST-SD females a significant increase （P 〈 0.05） in expression levels of leptin （Ob-Rt） mRNA receptor gene, in ovaries was noted. Aldosteron （Nr3c2） and vasopressin （AVP） mRNA receptor expression genes levels were significantly （P 〈 0.05） increased in both LD- and SD- ST- males.
