首页 > 最新文献

Cellular Oncology最新文献

英文 中文
LILRB2 promotes immune escape in breast cancer cells via enhanced HLA-A degradation. LILRB2 通过增强 HLA-A 降解促进乳腺癌细胞的免疫逃逸。
IF 6.6 2区 医学 Q1 Medicine Pub Date : 2024-04-24 DOI: 10.1007/s13402-024-00947-5
Zhiyuan Jiang, Qianru Huang, Yujie Chang, Yiran Qiu, Hao Cheng, Mengdi Yang, Shunyi Ruan, Suyuan Ji, Jing Sun, Zhi-yu Wang, Shengyuan Xu, Rui Liang, Xueyu Dai, Kejin Wu, Bin Li, Dan Li, Hui Zhao
{"title":"LILRB2 promotes immune escape in breast cancer cells via enhanced HLA-A degradation.","authors":"Zhiyuan Jiang, Qianru Huang, Yujie Chang, Yiran Qiu, Hao Cheng, Mengdi Yang, Shunyi Ruan, Suyuan Ji, Jing Sun, Zhi-yu Wang, Shengyuan Xu, Rui Liang, Xueyu Dai, Kejin Wu, Bin Li, Dan Li, Hui Zhao","doi":"10.1007/s13402-024-00947-5","DOIUrl":"https://doi.org/10.1007/s13402-024-00947-5","url":null,"abstract":"","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140661591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Exploring the impact of PDGFD in osteosarcoma metastasis through single-cell sequencing analysis. 通过单细胞测序分析探索 PDGFD 对骨肉瘤转移的影响
IF 6.6 2区 医学 Q1 Medicine Pub Date : 2024-04-23 DOI: 10.1007/s13402-024-00949-3
Yujing Huang, Dongyan Cao, Manxue Zhang, Yue Yang, Gengming Niu, Lina Tang, Zan Shen, Zhichang Zhang, Yueqing Bai, Daliu Min, Aina He
{"title":"Exploring the impact of PDGFD in osteosarcoma metastasis through single-cell sequencing analysis.","authors":"Yujing Huang, Dongyan Cao, Manxue Zhang, Yue Yang, Gengming Niu, Lina Tang, Zan Shen, Zhichang Zhang, Yueqing Bai, Daliu Min, Aina He","doi":"10.1007/s13402-024-00949-3","DOIUrl":"https://doi.org/10.1007/s13402-024-00949-3","url":null,"abstract":"","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140666395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Chordoma cells possess bone-dissolving activity at the bone invasion front. 脊索瘤细胞在骨侵袭前沿具有溶骨活性。
IF 6.6 2区 医学 Q1 Medicine Pub Date : 2024-04-23 DOI: 10.1007/s13402-024-00946-6
Katsuhiro Kawaai, Yumiko Oishi, Yukiko Kuroda, R. Tamura, Masahiro Toda, Koichi Matsuo
{"title":"Chordoma cells possess bone-dissolving activity at the bone invasion front.","authors":"Katsuhiro Kawaai, Yumiko Oishi, Yukiko Kuroda, R. Tamura, Masahiro Toda, Koichi Matsuo","doi":"10.1007/s13402-024-00946-6","DOIUrl":"https://doi.org/10.1007/s13402-024-00946-6","url":null,"abstract":"","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140667236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Correction to: Microbial metabolite trimethylamine-N-oxide induces intestinal carcinogenesis through inhibiting farnesoid X receptor signaling 更正为微生物代谢物三甲胺-N-氧化物通过抑制法尼类固醇 X 受体信号传导诱导肠癌发生
IF 6.6 2区 医学 Q1 Medicine Pub Date : 2024-04-16 DOI: 10.1007/s13402-024-00937-7
Wanru Zhang, Xiali Qin, Kexin Zhang, Jiahui Ma, Mengfan Li, Ge Jin, Xiang Liu, Sinan Wang, Bangmao Wang, Jing Wu, Tianyu Liu, Weilong Zhong, Hailong Cao
{"title":"Correction to: Microbial metabolite trimethylamine-N-oxide induces intestinal carcinogenesis through inhibiting farnesoid X receptor signaling","authors":"Wanru Zhang, Xiali Qin, Kexin Zhang, Jiahui Ma, Mengfan Li, Ge Jin, Xiang Liu, Sinan Wang, Bangmao Wang, Jing Wu, Tianyu Liu, Weilong Zhong, Hailong Cao","doi":"10.1007/s13402-024-00937-7","DOIUrl":"https://doi.org/10.1007/s13402-024-00937-7","url":null,"abstract":"","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140613794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Integrated analysis of single-cell RNA-seq and bulk RNA-seq reveals immune suppression subtypes and establishes a novel signature for determining the prognosis in lung adenocarcinoma 单细胞RNA-seq和大体RNA-seq的整合分析揭示了免疫抑制亚型,并建立了用于确定肺腺癌预后的新型特征
IF 6.6 2区 医学 Q1 Medicine Pub Date : 2024-04-15 DOI: 10.1007/s13402-024-00948-4
Shengqiang Mao, Yilong Wang, Ningning Chao, Lingyan Zeng, Li Zhang

Background

Lung adenocarcinoma (LUAD) is the most common histological type of lung cancer with lower survival rates. Recent advancements in targeted therapies and immunotherapies targeting immune checkpoints have achieved remarkable success, there is still a large percentage of LUAD that lacks available therapeutic options. Due to tumor heterogeneity, the diagnosis and treatment of LUAD are challenging. Exploring the biology of LUAD and identifying new biomarker and therapeutic targets options are essential.

Method

We performed single-cell RNA sequencing (scRNA-seq) of 6 paired primary and adjacent LUAD tissues, and integrative omics analysis of the scRNA-seq, bulk RNA-seq and whole-exome sequencing data revealed molecular subtype characteristics. Our experimental results confirm that CDC25C gene can serve as a potential marker for poor prognosis in LUAD.

Results

We investigated aberrant gene expression in diverse cell types in LUAD via the scRNA-seq data. Moreover, multi-omics clustering revealed four subgroups defined by transcriptional profile and molecular subtype 4 (MS4) with poor survival probability, and immune cell infiltration signatures revealed that MS4 tended to be the immunosuppressive subtype. Our study revealed that the CDC25C gene can be a distinct prognostic biomarker that indicates immune infiltration levels and response to immunotherapy in LUAD patients. Our experimental results concluded that CDC25C expression affects lung cancer cell invasion and migration, might play a key role in regulating Epithelial-Mesenchymal Transition (EMT) pathways.

Conclusions

Our multi-omics result revealed a comprehensive set of molecular attributes associated with prognosis-related genes in LUAD at the cellular and tissue level. Identification of a subtype of immunosuppressive TME and prognostic signature for LUAD. We identified the cell cycle regulation gene CDC25C affects lung cancer cell invasion and migration, which can be used as a potential biomarker for LUAD.

背景肺腺癌(LUAD)是肺癌中最常见的组织学类型,生存率较低。近年来,靶向治疗和针对免疫检查点的免疫疗法取得了显著进展,但仍有很大一部分肺腺癌患者缺乏可供选择的治疗方案。由于肿瘤的异质性,LUAD 的诊断和治疗具有挑战性。方法我们对6个配对的原发性和相邻的LUAD组织进行了单细胞RNA测序(scRNA-seq),并对scRNA-seq、大量RNA-seq和全外显子组测序数据进行了整合性全局分析,揭示了分子亚型特征。我们的实验结果证实,CDC25C基因可作为LUAD预后不良的潜在标志物。结果我们通过scRNA-seq数据研究了LUAD中不同细胞类型的异常基因表达。此外,多组学聚类发现了四个由转录谱和分子亚型4(MS4)定义的亚组,这些亚组的生存概率较低,免疫细胞浸润特征显示MS4倾向于免疫抑制亚型。我们的研究发现,CDC25C基因可作为一种独特的预后生物标志物,指示LUAD患者的免疫浸润水平和对免疫疗法的反应。我们的实验结果表明,CDC25C的表达影响肺癌细胞的侵袭和迁移,可能在调控上皮-间质转化(EMT)通路中发挥关键作用。确定了免疫抑制性 TME 亚型和 LUAD 的预后特征。我们发现细胞周期调控基因 CDC25C 影响肺癌细胞的侵袭和迁移,可作为 LUAD 的潜在生物标志物。
{"title":"Integrated analysis of single-cell RNA-seq and bulk RNA-seq reveals immune suppression subtypes and establishes a novel signature for determining the prognosis in lung adenocarcinoma","authors":"Shengqiang Mao, Yilong Wang, Ningning Chao, Lingyan Zeng, Li Zhang","doi":"10.1007/s13402-024-00948-4","DOIUrl":"https://doi.org/10.1007/s13402-024-00948-4","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Lung adenocarcinoma (LUAD) is the most common histological type of lung cancer with lower survival rates. Recent advancements in targeted therapies and immunotherapies targeting immune checkpoints have achieved remarkable success, there is still a large percentage of LUAD that lacks available therapeutic options. Due to tumor heterogeneity, the diagnosis and treatment of LUAD are challenging. Exploring the biology of LUAD and identifying new biomarker and therapeutic targets options are essential.</p><h3 data-test=\"abstract-sub-heading\">Method</h3><p>We performed single-cell RNA sequencing (scRNA-seq) of 6 paired primary and adjacent LUAD tissues, and integrative omics analysis of the scRNA-seq, bulk RNA-seq and whole-exome sequencing data revealed molecular subtype characteristics. Our experimental results confirm that <i>CDC25C</i> gene can serve as a potential marker for poor prognosis in LUAD.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>We investigated aberrant gene expression in diverse cell types in LUAD via the scRNA-seq data. Moreover, multi-omics clustering revealed four subgroups defined by transcriptional profile and molecular subtype 4 (MS4) with poor survival probability, and immune cell infiltration signatures revealed that MS4 tended to be the immunosuppressive subtype. Our study revealed that the <i>CDC25C</i> gene can be a distinct prognostic biomarker that indicates immune infiltration levels and response to immunotherapy in LUAD patients. Our experimental results concluded that <i>CDC25C</i> expression affects lung cancer cell invasion and migration, might play a key role in regulating Epithelial-Mesenchymal Transition (EMT) pathways.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>Our multi-omics result revealed a comprehensive set of molecular attributes associated with prognosis-related genes in LUAD at the cellular and tissue level. Identification of a subtype of immunosuppressive TME and prognostic signature for LUAD. We identified the cell cycle regulation gene <i>CDC25C</i> affects lung cancer cell invasion and migration, which can be used as a potential biomarker for LUAD.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140587090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Establishment, characterization, and biobanking of 36 pancreatic cancer organoids: prediction of metastasis in resectable pancreatic cancer 36 个胰腺癌器官组织的建立、特征描述和生物库:可切除胰腺癌的转移预测
IF 6.6 2区 医学 Q1 Medicine Pub Date : 2024-04-15 DOI: 10.1007/s13402-024-00939-5
Soon-Chan Kim, Ha-Young Seo, Ja-Oh Lee, Ju Eun Maeng, Young-Kyoung Shin, Sang Hyub Lee, Jin-Young Jang, Ja-Lok Ku

Purpose

Early dissemination of primary pancreatic ductal adenocarcinoma (PDAC) is the main cause of dismal prognosis as it highly limits possible treatment options. A number of PDAC patients experience distant metastasis even after treatment due to the metastatic clones. We aimed to demonstrate the molecular architecture of borderline resectable PDAC manifests cancer dissemination of PDAC.

Methods

Here, 36 organoids isolated from primary tumor masses of PDAC patients with diverse metastatic statues are presented. Whole-exome sequencing and RNA sequencing were performed and drug responses to clinically relevant 18 compounds were assessed.

Results

Our results revealed that borderline resectable PDAC organoids exhibited distinct patterns according to their metastatic potency highlighted by multiple genetic and transcriptional factors and strong variances in drug responses.

Conclusions

These data suggest that the presence of metastatic PDAC can be identified by integrating molecular compositions and drug responses of borderline resectable PDAC.

目的原发性胰腺导管腺癌(PDAC)的早期播散是预后不良的主要原因,因为它极大地限制了可能的治疗方案。许多 PDAC 患者在接受治疗后仍会因转移克隆而发生远处转移。我们旨在证明边缘可切除PDAC的分子结构表现出PDAC的癌症扩散。结果我们的研究结果表明,边缘可切除的 PDAC 有机体根据其转移能力表现出不同的模式,突出表现为多种遗传和转录因子以及药物反应的强烈差异。
{"title":"Establishment, characterization, and biobanking of 36 pancreatic cancer organoids: prediction of metastasis in resectable pancreatic cancer","authors":"Soon-Chan Kim, Ha-Young Seo, Ja-Oh Lee, Ju Eun Maeng, Young-Kyoung Shin, Sang Hyub Lee, Jin-Young Jang, Ja-Lok Ku","doi":"10.1007/s13402-024-00939-5","DOIUrl":"https://doi.org/10.1007/s13402-024-00939-5","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose</h3><p>Early dissemination of primary pancreatic ductal adenocarcinoma (PDAC) is the main cause of dismal prognosis as it highly limits possible treatment options. A number of PDAC patients experience distant metastasis even after treatment due to the metastatic clones. We aimed to demonstrate the molecular architecture of borderline resectable PDAC manifests cancer dissemination of PDAC.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Here, 36 organoids isolated from primary tumor masses of PDAC patients with diverse metastatic statues are presented. Whole-exome sequencing and RNA sequencing were performed and drug responses to clinically relevant 18 compounds were assessed.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Our results revealed that borderline resectable PDAC organoids exhibited distinct patterns according to their metastatic potency highlighted by multiple genetic and transcriptional factors and strong variances in drug responses.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>These data suggest that the presence of metastatic PDAC can be identified by integrating molecular compositions and drug responses of borderline resectable PDAC.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140579521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The emerging role of CARM1 in cancer CARM1 在癌症中的新作用
IF 6.6 2区 医学 Q1 Medicine Pub Date : 2024-04-15 DOI: 10.1007/s13402-024-00943-9
Zizhuo Xie, Yuan Tian, Xiaohan Guo, Na Xie

Coactivator-associated arginine methyltransferase 1 (CARM1), pivotal for catalyzing arginine methylation of histone and non-histone proteins, plays a crucial role in developing various cancers. CARM1 was initially recognized as a transcriptional coregulator by orchestrating chromatin remodeling, transcription regulation, mRNA splicing and stability. This diverse functionality contributes to the recruitment of transcription factors that foster malignancies. Going beyond its established involvement in transcriptional control, CARM1-mediated methylation influences a spectrum of biological processes, including the cell cycle, metabolism, autophagy, redox homeostasis, and inflammation. By manipulating these physiological functions, CARM1 becomes essential in critical processes such as tumorigenesis, metastasis, and therapeutic resistance. Consequently, it emerges as a viable target for therapeutic intervention and a possible biomarker for medication response in specific cancer types. This review provides a comprehensive exploration of the various physiological functions of CARM1 in the context of cancer. Furthermore, we discuss potential CARM1-targeting pharmaceutical interventions for cancer therapy.

共激活子相关精氨酸甲基转移酶 1(CARM1)在催化组蛋白和非组蛋白的精氨酸甲基化方面起着关键作用,在各种癌症的发病过程中发挥着重要作用。CARM1 最初被认为是一种转录核心调节器,可协调染色质重塑、转录调节、mRNA 剪接和稳定性。这种多样化的功能有助于转录因子的招募,从而诱发恶性肿瘤。CARM1 介导的甲基化不仅参与转录调控,还影响一系列生物过程,包括细胞周期、新陈代谢、自噬、氧化还原平衡和炎症。通过操纵这些生理功能,CARM1 在肿瘤发生、转移和抗药性等关键过程中变得至关重要。因此,CARM1 成为治疗干预的可行靶点,并可能成为特定癌症类型中药物反应的生物标志物。本综述全面探讨了 CARM1 在癌症中的各种生理功能。此外,我们还讨论了潜在的以 CARM1 为靶点的癌症治疗药物干预。
{"title":"The emerging role of CARM1 in cancer","authors":"Zizhuo Xie, Yuan Tian, Xiaohan Guo, Na Xie","doi":"10.1007/s13402-024-00943-9","DOIUrl":"https://doi.org/10.1007/s13402-024-00943-9","url":null,"abstract":"<p>Coactivator-associated arginine methyltransferase 1 (CARM1), pivotal for catalyzing arginine methylation of histone and non-histone proteins, plays a crucial role in developing various cancers. CARM1 was initially recognized as a transcriptional coregulator by orchestrating chromatin remodeling, transcription regulation, mRNA splicing and stability. This diverse functionality contributes to the recruitment of transcription factors that foster malignancies. Going beyond its established involvement in transcriptional control, CARM1-mediated methylation influences a spectrum of biological processes, including the cell cycle, metabolism, autophagy, redox homeostasis, and inflammation. By manipulating these physiological functions, CARM1 becomes essential in critical processes such as tumorigenesis, metastasis, and therapeutic resistance. Consequently, it emerges as a viable target for therapeutic intervention and a possible biomarker for medication response in specific cancer types. This review provides a comprehensive exploration of the various physiological functions of CARM1 in the context of cancer. Furthermore, we discuss potential CARM1-targeting pharmaceutical interventions for cancer therapy.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140579410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Downregulation of GPX8 in hepatocellular carcinoma: impact on tumor stemness and migration 肝细胞癌中 GPX8 的下调:对肿瘤干性和迁移的影响
IF 6.6 2区 医学 Q1 Medicine Pub Date : 2024-04-12 DOI: 10.1007/s13402-024-00934-w
Chen-Yang Tao, Xiao-Ling Wu, Shu-Shu Song, Zheng Tang, Yu-Fu Zhou, Meng-Xin Tian, Xi-Fei Jiang, Yuan Fang, Gui-Qi Zhu, Run Huang, Wei-Feng Qu, Jun Gao, Tian-Hao Chu, Rui Yang, Jia-Feng Chen, Qian-Fu Zhao, Zhen-Bin Ding, Zhi Dai, Jian Zhou, Wei-Ren Liu, Ying-Hong Shi, Jia Fan

Purpose

GPX8, which is found in the endoplasmic reticulum lumen, is a member of the Glutathione Peroxidases (GPXs) family. Its role in hepatocellular carcinoma (HCC) is unknown.

Methods

Immunohistochemical staining was used to detect the protein levels of GPX8 in HCC tissue microarrays. A short hairpin RNA lentivirus was used to knock down GPX8, and the main signaling pathways were investigated using transcriptome sequencing and a phosphorylated kinase array. The sphere formation assays, cloning-formation assays and cell migration assays were used to evaluate the stemness and migration ability of HCC cells. Identifying the GPX8-interacting proteins was accomplished through immunoprecipitation and protein mass spectrometry.

Results

The GPX8 protein levels were downregulated in HCC patients. Low expression of GPX8 protein was related to early recurrence and poor prognosis in HCC patients. GPX8 knockdown could enhance the stemness and migration ability of HCC cells. Consistently, Based on transcriptome analysis, multiple signaling pathways that include the PI3K-AKT and signaling pathways that regulate the pluripotency of stem cells, were activated after GPX8 knockdown. The downregulation of GPX8 could increase the expression of the tumor stemness markers KLF4, OCT4, and CD133. The in vivo downregulation of GPX8 could also promote the subcutaneous tumor-forming and migration ability of HCC cells. MK-2206, which is a small-molecule inhibitor of AKT, could reverse the tumor-promoting effects both in vivo and in vitro. We discovered that GPX8 and the 71-kDa heat shock cognate protein (Hsc70) have a direct interaction. The phosphorylation of AKT encouraged the translocation of Hsc70 into the nucleus and the expression of the PI3K p110 subunit, thereby increasing the downregulation of GPX8.

Conclusion

The findings from this study demonstrate the anticancer activity of GPX8 in HCC by inactivating the Hsc70/AKT pathway. The results suggest a possible therapeutic target for HCC.

目的GPX8存在于内质网腔中,是谷胱甘肽过氧化物酶(GPXs)家族的成员之一。方法采用免疫组织化学染色法检测 HCC 组织芯片中 GPX8 的蛋白水平。使用短发夹 RNA 慢病毒敲除 GPX8,并使用转录组测序和磷酸化激酶阵列研究主要信号通路。球形成试验、克隆形成试验和细胞迁移试验用于评估HCC细胞的干性和迁移能力。通过免疫沉淀和蛋白质质谱鉴定与 GPX8 相互作用的蛋白质。GPX8 蛋白的低表达与 HCC 患者的早期复发和预后不良有关。GPX8 基因敲除可增强 HCC 细胞的干性和迁移能力。同样,根据转录组分析,GPX8敲除后,包括PI3K-AKT和调控干细胞多能性的信号通路在内的多种信号通路被激活。GPX8的下调可增加肿瘤干性标志物KLF4、OCT4和CD133的表达。在体内下调GPX8还能促进HCC细胞的皮下肿瘤形成和迁移能力。MK-2206是一种AKT小分子抑制剂,它能逆转体内和体外的促瘤效应。我们发现 GPX8 与 71 kDa 热休克同源蛋白(Hsc70)有直接的相互作用。AKT的磷酸化促进了Hsc70向细胞核的转位和PI3K p110亚基的表达,从而增加了GPX8的下调。这些结果表明 GPX8 是治疗 HCC 的可能靶点。
{"title":"Downregulation of GPX8 in hepatocellular carcinoma: impact on tumor stemness and migration","authors":"Chen-Yang Tao, Xiao-Ling Wu, Shu-Shu Song, Zheng Tang, Yu-Fu Zhou, Meng-Xin Tian, Xi-Fei Jiang, Yuan Fang, Gui-Qi Zhu, Run Huang, Wei-Feng Qu, Jun Gao, Tian-Hao Chu, Rui Yang, Jia-Feng Chen, Qian-Fu Zhao, Zhen-Bin Ding, Zhi Dai, Jian Zhou, Wei-Ren Liu, Ying-Hong Shi, Jia Fan","doi":"10.1007/s13402-024-00934-w","DOIUrl":"https://doi.org/10.1007/s13402-024-00934-w","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose</h3><p>GPX8, which is found in the endoplasmic reticulum lumen, is a member of the Glutathione Peroxidases (GPXs) family. Its role in hepatocellular carcinoma (HCC) is unknown.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Immunohistochemical staining was used to detect the protein levels of GPX8 in HCC tissue microarrays. A short hairpin RNA lentivirus was used to knock down GPX8, and the main signaling pathways were investigated using transcriptome sequencing and a phosphorylated kinase array. The sphere formation assays, cloning-formation assays and cell migration assays were used to evaluate the stemness and migration ability of HCC cells. Identifying the GPX8-interacting proteins was accomplished through immunoprecipitation and protein mass spectrometry.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>The GPX8 protein levels were downregulated in HCC patients. Low expression of GPX8 protein was related to early recurrence and poor prognosis in HCC patients. GPX8 knockdown could enhance the stemness and migration ability of HCC cells. Consistently, Based on transcriptome analysis, multiple signaling pathways that include the PI3K-AKT and signaling pathways that regulate the pluripotency of stem cells, were activated after GPX8 knockdown. The downregulation of GPX8 could increase the expression of the tumor stemness markers KLF4, OCT4, and CD133. The in vivo downregulation of GPX8 could also promote the subcutaneous tumor-forming and migration ability of HCC cells. MK-2206, which is a small-molecule inhibitor of AKT, could reverse the tumor-promoting effects both in vivo and in vitro. We discovered that GPX8 and the 71-kDa heat shock cognate protein (Hsc70) have a direct interaction. The phosphorylation of AKT encouraged the translocation of Hsc70 into the nucleus and the expression of the PI3K p110 subunit, thereby increasing the downregulation of GPX8.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>The findings from this study demonstrate the anticancer activity of GPX8 in HCC by inactivating the Hsc70/AKT pathway. The results suggest a possible therapeutic target for HCC.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140579404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Dexmedetomidine promotes colorectal cancer progression via Piwil2 signaling 右美托咪定通过 Piwil2 信号促进结直肠癌进展
IF 6.6 2区 医学 Q1 Medicine Pub Date : 2024-04-09 DOI: 10.1007/s13402-024-00944-8
Jing Dong, Ji Che, Yuanyuan Wu, Yixu Deng, Xuliang Jiang, Zhiyong He, Jun Zhang

Purpose

α2-adrenoceptor agonist dexmedetomidine (DEX) has been reported to promote tumorigenesis. Stem-cell protein Piwil2 is associated with cancer progression. Whether Piwil2 plays a role in tumor-promoting effects of DEX is unknown.

Methods

We examined the expression of Piwil2 in human colorectal cancer (CRC) cell lines with/without DEX treatment. We also studied the roles of Piwil2 in proliferation, invasion, migration, as well as expressions of epithelial-mesenchymal transition (EMT)-related proteins in DEX-treated in vitro and in vivo CRC models. And the experiments with genetic and pharmacological treatments were conducted to investigate the underlying molecular mechanism.

Results

RNA-sequencing (RNA-seq) analysis found Piwil2 is one of most upregulated genes upon DEX treatment in CRC cells. Furthermore, Piwil2 protein levels significantly increased in DEX-treated CRC cancer cells, which promoted proliferation, invasion, and migration in both CRC cell lines and human tumor xenografts model. Mechanistically, DEX increased nuclear factor E2-related factor 2 (Nrf2) expression, which enhanced Piwil2 transcription via binding to its promoter. Furthermore, in vitro experiments with Piwil2 knockdown or Siah2 inhibition indicated that DEX promoted EMT process and tumorigenesis through Siah2/PHD3/HIF1α pathway. The experiments with another α2-adrenoceptor agonist Brimonidine and antagonists yohimbine and atipamezole also suggested the role of Piwil2 signaling in tumor-promoting effects via an α2 adrenoceptor-dependent manner.

Conclusion

DEX promotes CRC progression may via activating α2 adrenoceptor-dependent Nrf2/Piwil2/Siah2 pathway and thus EMT process. Our work provides a novel insight into the mechanism underlying tumor-promoting effects of α2-adrenoceptor agonists.

目的 据报道,α2-肾上腺素受体激动剂右美托咪定(DEX)可促进肿瘤发生。干细胞蛋白 Piwil2 与癌症进展有关。我们检测了在使用/不使用 DEX 治疗的人类结直肠癌细胞系中 Piwil2 的表达。我们还研究了 Piwil2 在经 DEX 处理的体外和体内 CRC 模型中的增殖、侵袭、迁移以及上皮-间质转化(EMT)相关蛋白表达中的作用。结果RNA序列(RNA-seq)分析发现,Piwil2是DEX处理CRC细胞后上调最多的基因之一。此外,DEX 处理的 CRC 癌细胞中 Piwil2 蛋白水平显著升高,促进了 CRC 细胞系和人肿瘤异种移植模型的增殖、侵袭和迁移。从机理上讲,DEX增加了核因子E2相关因子2(Nrf2)的表达,而Nrf2通过与其启动子结合增强了Piwil2的转录。此外,敲除Piwil2或抑制Siah2的体外实验表明,DEX通过Siah2/PHD3/HIF1α途径促进EMT过程和肿瘤发生。用另一种α2肾上腺素受体激动剂溴莫尼定以及拮抗剂育亨宾和阿替巴唑进行的实验也表明,Piwil2信号传导通过α2肾上腺素受体依赖的方式在肿瘤促进作用中发挥作用。我们的研究为了解α2肾上腺素受体激动剂的肿瘤促进作用机制提供了新的视角。
{"title":"Dexmedetomidine promotes colorectal cancer progression via Piwil2 signaling","authors":"Jing Dong, Ji Che, Yuanyuan Wu, Yixu Deng, Xuliang Jiang, Zhiyong He, Jun Zhang","doi":"10.1007/s13402-024-00944-8","DOIUrl":"https://doi.org/10.1007/s13402-024-00944-8","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose</h3><p>α2-adrenoceptor agonist dexmedetomidine (DEX) has been reported to promote tumorigenesis. Stem-cell protein Piwil2 is associated with cancer progression. Whether Piwil2 plays a role in tumor-promoting effects of DEX is unknown.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>We examined the expression of Piwil2 in human colorectal cancer (CRC) cell lines with/without DEX treatment. We also studied the roles of Piwil2 in proliferation, invasion, migration, as well as expressions of epithelial-mesenchymal transition (EMT)-related proteins in DEX-treated in vitro and in vivo CRC models. And the experiments with genetic and pharmacological treatments were conducted to investigate the underlying molecular mechanism.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>RNA-sequencing (RNA-seq) analysis found Piwil2 is one of most upregulated genes upon DEX treatment in CRC cells. Furthermore, Piwil2 protein levels significantly increased in DEX-treated CRC cancer cells, which promoted proliferation, invasion, and migration in both CRC cell lines and human tumor xenografts model. Mechanistically, DEX increased nuclear factor E2-related factor 2 (Nrf2) expression, which enhanced Piwil2 transcription via binding to its promoter. Furthermore, in vitro experiments with Piwil2 knockdown or Siah2 inhibition indicated that DEX promoted EMT process and tumorigenesis through Siah2/PHD3/HIF1α pathway. The experiments with another α2-adrenoceptor agonist Brimonidine and antagonists yohimbine and atipamezole also suggested the role of Piwil2 signaling in tumor-promoting effects via an α2 adrenoceptor-dependent manner.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>DEX promotes CRC progression may via activating α2 adrenoceptor-dependent Nrf2/Piwil2/Siah2 pathway and thus EMT process. Our work provides a novel insight into the mechanism underlying tumor-promoting effects of α2-adrenoceptor agonists.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140579523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Hedgehog ligand and receptor cooperatively regulate EGFR stability and activity in non-small cell lung cancer 刺猬配体和受体协同调控非小细胞肺癌表皮生长因子受体的稳定性和活性
IF 6.6 2区 医学 Q1 Medicine Pub Date : 2024-04-03 DOI: 10.1007/s13402-024-00938-6
Aidi Huang, Junyao Cheng, Yuan Zhan, Feifei Zhou, Yanlu Xuan, Yiting Wang, Qingjie Chen, Hailong Wang, Xinping Xu, Shiwen Luo, Minzhang Cheng

Purpose

The hyperactivation of epidermal growth factor receptor (EGFR) plays a crucial role in non-small cell lung cancer (NSCLC). Hedgehog (Hh) signaling has been implicated in the tumorigenesis and progression of various cancers, however, its function in NSCLC cells remains controversial. Herein, we present a novel finding that challenges the current understanding of Hh signaling in tumor growth.

Methods

Expression of Hh ligands and receptor were assessed using TCGA datasets, immunoblotting and immunohistochemical. Biological function of Hh ligands and receptor in NSCLC were tested using colony formation, cell count kit-8 (CCK-8) and xenograft assays. Biochemical effect of Hh ligands and receptor on regulating EGFR stability and activity were checked via immunoblotting.

Results

Expression of Hh ligands and receptor was suppressed in NSCLC tissues, and the lower expression levels of these genes were associated with poor prognosis. Ptch1 binds to EGFR and facilitates its poly-ubiquitylation and degradation independent of downstream transcriptional signaling. Moreover, Hh ligands cooperate with Ptch1 to regulate the protein stability and activity of EGFR. This unique mechanism leads to a suppressive effect on NSCLC tumor growth.

Conclusion

Non-canonical Hh signaling pathway, involving cooperation between Hh ligands and their receptor Ptch1, facilitates the degradation of EGFR and attenuates its activity in NSCLC. These findings provide novel insights into the regulation of EGFR protein stability and activity, offer new diagnostic indicators for molecular typing of NSCLC and identify potential targets for targeted therapy of this challenging disease.

目的 表皮生长因子受体(EGFR)的过度激活在非小细胞肺癌(NSCLC)中起着至关重要的作用。刺猬(Hh)信号与多种癌症的肿瘤发生和进展有关,但其在非小细胞肺癌细胞中的功能仍存在争议。在此,我们提出了一个新发现,挑战了目前对Hh信号在肿瘤生长中的作用的理解。方法使用TCGA数据集、免疫印迹法和免疫组化法评估Hh配体和受体的表达。使用集落形成、细胞计数试剂盒-8(CCK-8)和异种移植试验检测了Hh配体和受体在NSCLC中的生物学功能。结果Hh配体和受体在NSCLC组织中的表达受到抑制,这些基因的低表达水平与预后不良有关。Ptch1与表皮生长因子受体结合,促进其多泛素化和降解,而不受下游转录信号的影响。此外,Hh 配体与 Ptch1 合作调节表皮生长因子受体的蛋白稳定性和活性。结论 非规范 Hh 信号通路涉及 Hh 配体及其受体 Ptch1 之间的合作,促进了表皮生长因子受体的降解并削弱了其在 NSCLC 中的活性。这些发现为表皮生长因子受体蛋白稳定性和活性的调控提供了新的见解,为 NSCLC 的分子分型提供了新的诊断指标,并为这种具有挑战性的疾病的靶向治疗确定了潜在的目标。
{"title":"Hedgehog ligand and receptor cooperatively regulate EGFR stability and activity in non-small cell lung cancer","authors":"Aidi Huang, Junyao Cheng, Yuan Zhan, Feifei Zhou, Yanlu Xuan, Yiting Wang, Qingjie Chen, Hailong Wang, Xinping Xu, Shiwen Luo, Minzhang Cheng","doi":"10.1007/s13402-024-00938-6","DOIUrl":"https://doi.org/10.1007/s13402-024-00938-6","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose</h3><p>The hyperactivation of epidermal growth factor receptor (EGFR) plays a crucial role in non-small cell lung cancer (NSCLC). Hedgehog (Hh) signaling has been implicated in the tumorigenesis and progression of various cancers, however, its function in NSCLC cells remains controversial. Herein, we present a novel finding that challenges the current understanding of Hh signaling in tumor growth.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Expression of Hh ligands and receptor were assessed using TCGA datasets, immunoblotting and immunohistochemical. Biological function of Hh ligands and receptor in NSCLC were tested using colony formation, cell count kit-8 (CCK-8) and xenograft assays. Biochemical effect of Hh ligands and receptor on regulating EGFR stability and activity were checked via immunoblotting.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Expression of Hh ligands and receptor was suppressed in NSCLC tissues, and the lower expression levels of these genes were associated with poor prognosis. Ptch1 binds to EGFR and facilitates its poly-ubiquitylation and degradation independent of downstream transcriptional signaling. Moreover, Hh ligands cooperate with Ptch1 to regulate the protein stability and activity of EGFR. This unique mechanism leads to a suppressive effect on NSCLC tumor growth.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>Non-canonical Hh signaling pathway, involving cooperation between Hh ligands and their receptor Ptch1, facilitates the degradation of EGFR and attenuates its activity in NSCLC. These findings provide novel insights into the regulation of EGFR protein stability and activity, offer new diagnostic indicators for molecular typing of NSCLC and identify potential targets for targeted therapy of this challenging disease.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140579529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Cellular Oncology
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1