Cellular OncologyPub Date : 2024-04-15DOI: 10.1007/s13402-024-00948-4
Shengqiang Mao, Yilong Wang, Ningning Chao, Lingyan Zeng, Li Zhang
{"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":"16 1","pages":""},"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}
Cellular OncologyPub Date : 2024-04-15DOI: 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
{"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":"51 1","pages":""},"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}
Cellular OncologyPub Date : 2024-04-15DOI: 10.1007/s13402-024-00943-9
Zizhuo Xie, Yuan Tian, Xiaohan Guo, Na Xie
{"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":"12 1","pages":""},"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}
{"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":"48 1","pages":""},"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}
Cellular OncologyPub Date : 2024-04-09DOI: 10.1007/s13402-024-00944-8
Jing Dong, Ji Che, Yuanyuan Wu, Yixu Deng, Xuliang Jiang, Zhiyong He, Jun Zhang
{"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":"31 1","pages":""},"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}