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HPV16 E6/E7-mediated regulation of PiwiL1 expression induces tumorigenesis in cervical cancer cells. hpv16e6 / e7介导的PiwiL1表达调控诱导宫颈癌细胞的肿瘤发生
IF 6.6 2区 医学 Q1 Medicine Pub Date : 2024-06-01 Epub Date: 2023-12-01 DOI: 10.1007/s13402-023-00904-8
Midhunaraj Kunnummal, Pooja Sherly Raveendran, Budhaditya Basu, Sheri Vidya Rani, Riya Ann Paul, Krithiga Kuppusamy, Mary Angelin, Joby Issac, Jackson James, Ani V Das

Purpose: PiwiL1 has been reported to be over-expressed in many cancers. However, the molecular mechanism by which these proteins contribute to tumorigenesis and their regulation in cancer cells is still unclear. We intend to understand the role of PiwiL1 in tumorigenesis and also its regulation in cervical cells.

Methods: We studied the effect of loss of PiwiL1 function on tumor properties of cervical cancer cells in vitro and in vivo. Also we have looked into the effect of PiwiL1 overexpression in the malignant transformation of normal cells both in vitro and in vivo. Further RNA-seq and RIP-seq analyses were done to get insight of the direct and indirect targets of PiwiL1 in the cervical cancer cells.

Results: Here, we report that PiwiL1 is not only over-expressed, but also play a major role in tumor induction and progression. Abolition of PiwiL1 in CaSki cells led to a decrease in the tumor-associated properties, whereas, its upregulation conferred malignant transformation of normal HaCaT cells. Our study delineates a new link between HPV oncogenes, E6 and E7 with PiwiL1. p53 and E2F1 directly bind and differentially regulate PiwiL1 promoter in a context-dependant manner. Further, RNA-seq together with RIP-RNA-seq suggested a strong and direct role for PiwiL1 in promoting metastasis in cervical cancer cells.

Conclusion: Our study demonstrates that PiwiL1 act as an oncogene in cervical cancer by inducing tumor-associated properties and EMT pathway. The finding that HPV oncogenes, E6/E7 can positively regulate PiwiL1 suggests a possible mechanism behind HPV-mediated tumorigenesis in cervical cancer.

目的:据报道,PiwiL1在许多癌症中过表达。然而,这些蛋白参与肿瘤发生及其在癌细胞中的调控的分子机制尚不清楚。我们打算了解PiwiL1在肿瘤发生中的作用及其在宫颈细胞中的调节作用。方法:体外和体内研究PiwiL1功能缺失对宫颈癌细胞肿瘤特性的影响。此外,我们还在体外和体内研究了PiwiL1过表达对正常细胞恶性转化的影响。进一步进行RNA-seq和RIP-seq分析,以深入了解PiwiL1在宫颈癌细胞中的直接和间接靶点。结果:在这里,我们报道了PiwiL1不仅过表达,而且在肿瘤诱导和进展中发挥重要作用。CaSki细胞中PiwiL1的缺失导致肿瘤相关特性的降低,而其上调则导致正常HaCaT细胞的恶性转化。我们的研究描述了HPV癌基因E6和E7与PiwiL1之间的新联系。p53和E2F1以上下文依赖的方式直接结合并差异调节PiwiL1启动子。此外,RNA-seq和RIP-RNA-seq表明,PiwiL1在促进宫颈癌细胞转移中具有强烈而直接的作用。结论:我们的研究表明PiwiL1通过诱导肿瘤相关特性和EMT通路在宫颈癌中发挥致癌基因的作用。HPV致癌基因E6/E7可以正向调节PiwiL1,这一发现提示HPV介导宫颈癌肿瘤发生的可能机制。
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引用次数: 0
The development of in vitro organotypic 3D vulvar models to study tumor-stroma interaction and drug efficacy. 建立体外器官型3D外阴模型,研究肿瘤-基质相互作用及药物疗效。
IF 6.6 2区 医学 Q1 Medicine Pub Date : 2024-06-01 Epub Date: 2023-12-07 DOI: 10.1007/s13402-023-00902-w
Shidi Wu, Bertine W Huisman, Marion H Rietveld, Robert Rissmann, Maarten H Vermeer, Mariette I E van Poelgeest, Abdoelwaheb El Ghalbzouri

Background: Vulvar squamous cell carcinoma (VSCC) is a rare disease with a poor prognosis. To date, there's no proper in vitro modeling system for VSCC to study its pathogenesis or for drug evaluation.

Methods: We established healthy vulvar (HV)- and VSCC-like 3D full thickness models (FTMs) to observe the tumor-stroma interaction and their applicability for chemotherapeutic efficacy examination. VSCC-FTMs were developed by seeding VSCC tumor cell lines (A431 and HTB117) onto dermal matrices harboring two NF subtypes namely papillary fibroblasts (PFs) and reticular fibroblasts (RFs), or cancer-associated fibroblasts (CAFs) while HV-FTMs were constructed with primary keratinocytes and fibroblasts isolated from HV tissues.

Results: HV-FTMs highly resembled HV tissues in terms of epidermal morphogenesis, basement membrane formation and collagen deposition. When the dermal compartment shifted from PFs to RFs or CAFs in VSCC-FTMs, tumor cells demonstrated more proliferation, EMT induction and stemness. In contrast to PFs, RFs started to lose their phenotype and express robust CAF-markers α-SMA and COL11A1 under tumor cell signaling induction, indicating a favored 'RF-to-CAF' transition in VSCC tumor microenvironment (TME). Additionally, chemotherapeutic treatment with carboplatin and paclitaxel resulted in a significant reduction in tumor-load and invasion in VSCC-FTMs.

Conclusion: We successfully developed in vitro 3D vulvar models mimicking both healthy and tumorous conditions which serve as a promising tool for vulvar drug screening programs. Moreover, healthy fibroblasts demonstrate heterogeneity in terms of CAF-activation in VSCC TME which brings insights in the future development of novel CAF-based therapeutic strategies in VSCC.

背景:外阴鳞状细胞癌(VSCC)是一种罕见的疾病,预后较差。到目前为止,还没有合适的体外造模系统来研究VSCC的发病机制或进行药物评价。方法:建立健康外阴(HV)样和vscc样三维全层模型(FTMs),观察肿瘤与间质相互作用及其在化疗疗效检验中的适用性。VSCC- ftms是通过将VSCC肿瘤细胞系(A431和HTB117)播种到含有两种NF亚型(乳头状成纤维细胞(PFs)和网状成纤维细胞(RFs)或癌症相关成纤维细胞(CAFs)的真皮基质上培育而成的,而HV- ftms是用从HV组织中分离的原代角质形成细胞和成纤维细胞构建的。结果:HV- ftms在表皮形态发生、基底膜形成和胶原沉积等方面与HV组织高度相似。在VSCC-FTMs中,当真皮隔室从PFs转移到RFs或CAFs时,肿瘤细胞表现出更多的增殖、EMT诱导和干细胞性。与PFs相比,在肿瘤细胞信号传导诱导下,RFs开始失去其表型并表达强大的caf标记α-SMA和COL11A1,这表明VSCC肿瘤微环境(TME)中更倾向于“rf到caf”的转变。此外,卡铂和紫杉醇化疗可显著降低VSCC-FTMs的肿瘤负荷和侵袭。结论:我们成功地建立了模拟健康和肿瘤情况的体外3D外阴模型,为外阴药物筛选提供了一个有前途的工具。此外,健康成纤维细胞在VSCC TME中cafa活化方面表现出异质性,这为未来开发新的基于cafa的VSCC治疗策略提供了见解。
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引用次数: 0
Targeting Dectin-1 and or VISTA enhances anti-tumor immunity in melanoma but not colorectal cancer model. 靶向 Dectin-1 和或 VISTA 能增强黑色素瘤模型的抗肿瘤免疫力,但不能增强结直肠癌模型的抗肿瘤免疫力。
IF 6.6 2区 医学 Q1 Medicine Pub Date : 2024-04-26 DOI: 10.1007/s13402-024-00950-w
Siavash Mashhouri, Amirhossein Rahmati, Ako Azimi, Roy A Fava, Ismail Hassan Ismail, John Walker, Shokrollah Elahi
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引用次数: 0
Rituximab potentially improves clinical outcomes of CAR-T therapy for r/r B-ALL via sensitizing leukemia cells to CAR-T-mediated cytotoxicity and reducing CAR-T exhaustion. 利妥昔单抗可使白血病细胞对CAR-T介导的细胞毒性敏感并减少CAR-T衰竭,从而改善CAR-T疗法治疗r/r B-ALL的临床疗效。
IF 6.6 2区 医学 Q1 Medicine Pub Date : 2024-04-25 DOI: 10.1007/s13402-024-00945-7
Yangzi Li, Q. Cui, Sining Liu, Lingling Liu, Megyn Li, Jun Gao, Zheng Li, W. Cui, Xiaming Zhu, Liqing Kang, Lei Yu, Depei Wu, Xiaowen Tang
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引用次数: 0
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
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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":"9 8","pages":""},"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":"43 14","pages":""},"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":"14 1","pages":""},"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。
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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。
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引用次数: 0
期刊
Cellular Oncology
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