{"title":"ZC3H13 promotes autophagy in bladder cancer through m6A methylation modification of PJA2 and ubiquitination of KSR1.","authors":"Beibei Liu, Mengjie Chen, Yujie Liang, Zhijie Mei, Wei Sun, Wuyue Gao, Tiantian Zhang, Rui Wang, Yuanyuan Guo","doi":"10.1007/s13577-024-01155-x","DOIUrl":"10.1007/s13577-024-01155-x","url":null,"abstract":"<p><p>The N6-methyladenine (m6A) modification is the most common modification of messenger RNAs in eukaryotes and has crucial roles in multiple cancers, including bladder cancer (BLCA). This paper aimed to probe the molecular mechanism of zinc-finger CCCH-type containing 13 (ZC3H13)-mediated N6-methyladenine (m6A) modification in BLCA progression via autophagy. Differential expression of ZC3H13 in BLCA was analyzed by the bioinformatics database. ZC3H13 expression in BLCA tissues and cell lines was determined, and malignant behaviors of BLCA cells were examined in vitro and in vivo. ZC3H13 was decreased in BLCA tissues and cell lines relative to adjacent tissues and normal uroepithelial cells. ZC3H13 overexpression restricted BLCA cell growth in vitro and curbed BLCA development in vivo. ZC3H13 promoted the mRNA stability of paraja ring finger 2 (PJA2) through m6A modification, leading to the ubiquitination degradation of the kinase suppressor of Ras 1 (KSR1). Knockdown of PJA2 and overexpression of KSR1 reversed the inhibitory effect of ZC3H13 on BLCA progression. ZC3H13 degraded KSR1 through m6A modification of PJA2, promoted cell autophagy, and repressed BLCA progression. Overall, ZC3H13 promotes the mRNA stability of PJA2 through m6A modification to degrade KSR1, thereby promoting autophagy in BLCA.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 1","pages":"23"},"PeriodicalIF":3.4,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142774084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Molecular leveraging of HOX-embedded non-coding RNAs in the progression of acute myeloid leukemia.","authors":"Christine Wilson, Priyanka Swaroop, Sachin Kumar, Anita Chopra, Surender K Sharawat","doi":"10.1007/s13577-024-01149-9","DOIUrl":"10.1007/s13577-024-01149-9","url":null,"abstract":"<p><p>Acute myeloid leukemia (AML) is characterized by impaired differentiation of myeloid cells leading to hematopoietic failure. Despite advances, the molecular mechanisms driving AML remain incompletely understood, limiting the identification and targeting of critical vulnerabilities in leukemic cells. Homeobox (HOX) genes, encoding transcription factors essential for myeloid and lymphoid differentiation, are distributed across four clusters: HOXA (chromosome 7), HOXB (chromosome 17), HOXC (chromosome 12), and HOXD (chromosome 2). In addition to protein-coding sequences, HOX clusters encode non-coding RNAs (ncRNAs), which are functional as transcripts and do not translate into proteins. This is the first study wherein we comprehensively reviewed the literature for HOX-embedded ncRNAs, encompassing long non-coding RNAs (lncRNAs), microRNAs, circular RNAs (circRNAs), and piwiRNAs with a role in AML. To date, there is no evidence of circular RNAs and piwi RNAs encoded from the HOX gene clusters. Our review focuses on how leukemic cells harness the regulatory mechanisms of HOX-cluster-derived ncRNAs, (predominantly HOXA and HOXB) to modulate expression of HOX transcription factors facilitating leukemogenesis. HOX ncRNAs either regulate genes on the same chromosome (e.g., lncRNA HOTTIP) or influence expression of genes on different chromosomes (e.g., HOTAIR, HOX10-AS, miR-196b, and miR-10a). We discuss how specific HOX ncRNA networks are leveraged by leukemic cells, presenting an opportunity to explore targeted therapies and address the molecular heterogeneity of AML. Additionally, the aberrant expression of HOX ncRNAs such as HOXB derived ncRNAs in NPM1 mutated AML suggests their potential utility as improved biomarkers and for prognostication of patients with specific molecular aberrations.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 1","pages":"24"},"PeriodicalIF":3.4,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142774081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Establishment of a novel benign meningioma cell line spontaneously immortalized under hypoxic conditions.","authors":"Takaaki Ishikawa, Masahide Matsuda, Hiroshi Ishikawa, Junko Toyomura, Akihiro Ohyama, Noriaki Sakamoto, Alexander Zaboronok, Eiichi Ishikawa","doi":"10.1007/s13577-024-01151-1","DOIUrl":"10.1007/s13577-024-01151-1","url":null,"abstract":"<p><p>Meningiomas are the most frequent brain tumors, typically benign and curable by surgery. However, some patients experience repeated recurrences from residual tumors. To address such cases, the development of novel therapeutic options is crucial. For this purpose, the availability of cell lines that possess the characteristics of benign meningiomas is essential. Here, we established a benign meningioma cell line under 3% O<sub>2</sub> hypoxic conditions without the induction of immortalization genes. This cell line, named TKB-MEN2, has been stably grown for over two years with more than 20 passages. There were no hotspot telomerase reverse transcriptase (TERT) promoter mutations or cyclin-dependent kinase inhibitor 2A/2B (CDKN2A/2B) homozygous deletions, which are genetic features typical of malignant meningiomas. Cultured under hypoxic conditions, this cell line showed fewer characteristics of cellular senescence, such as morphological changes, IL-6 secretion, and lower senescence-associated b-galactosidase activity, compared to the same cell line cultured under 20% O<sub>2</sub> conditions. This immortalized non-transgenic cell line appears to reflect the characteristics of a genuine benign meningioma, potentially allowing the identification of new therapeutic targets and the development of novel therapies for benign meningiomas.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 1","pages":"22"},"PeriodicalIF":3.4,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142752083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Human CellPub Date : 2024-11-28DOI: 10.1007/s13577-024-01154-y
Juncun Yao, Li Sun, Feng Gao, Wei Zhu
{"title":"Mesenchymal stem/stromal cells: dedicator to maintain tumor homeostasis.","authors":"Juncun Yao, Li Sun, Feng Gao, Wei Zhu","doi":"10.1007/s13577-024-01154-y","DOIUrl":"10.1007/s13577-024-01154-y","url":null,"abstract":"<p><p>Mesenchymal stem/stromal cells (MSCs) act as a factor in tumor recurrence after drug treatment with their involvement observed in various cancer types. As a constituent of the tumor microenvironment (TME), MSCs not only provide support to tumor growth but also establish connections with diverse cell populations within the TME, serving as mediators linking different tumor-associated components. MSCs play an important role in maintaining tumor progression due to their stem cell properties and remarkable differentiation capacity. Given the intensification of tumor research and the encouraging results achieved in recent years,the aim of this article is to investigate the supportive role of MSCs in tumor cells as well as in various cellular and non-cellular components of the tumor microenvironment. Furthermore, the article shows that MSCs do not have a specific anatomical ecological niche and describes the contribution of MSCs to the maintenance of tumor homeostasis on the basis of homing, plasticity and tumor-forming properties. By elucidating the critical roles of different components of TME, this study provides a comprehensive understanding of tumor therapy and may offer new insights into defeating cancer.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 1","pages":"21"},"PeriodicalIF":3.4,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142741091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Establishment and characterization of NCC-GCTB14-C1 and NCC-GCTB15-C1: two novel patient-derived cell lines of giant cell tumor of bone.","authors":"Shuhei Iwata, Takuya Ono, Rei Noguchi, Julia Osaki, Yuki Adachi, Yomogi Shiota, Shintaro Iwata, Shogo Nishino, Akihiko Yoshida, Seiji Ohtori, Akira Kawai, Tadashi Kondo","doi":"10.1007/s13577-024-01150-2","DOIUrl":"10.1007/s13577-024-01150-2","url":null,"abstract":"<p><p>Giant cell tumor of bone (GCTB) is a rare bone tumor that is genetically characterized by a unique mutation in the H3-3A gene. Curative surgical resection is the standard treatment. Unfortunately, a considerable proportion of patients with GCTB have local recurrence and pulmonary metastasis after surgical treatment, and current chemotherapy treatments have shown non-effective. Considering the heterogeneity of the disease, patient-derived cancer models established from multiple cases are required. Therefore, we aimed to establish novel GCTB cell lines for use in preclinical studies. In this study, we successfully established two GCTB cell lines, NCC-GCTB14-C1 and NCC-GCTB15-C1. Both cell lines retained the genetic characteristics of the original tumors, constantly proliferated, and exhibited migratory activity. These cells formed spheroids with morphologically variable phenotypes. We found that they were compatible with chemosensitivity assays, and drug screening using these cell lines led to the identification of potential therapeutic candidates for GCTB. Therefore, NCC-GCTB14-C1 and NCC-GCTB15-C1 may be useful for elucidating the pathogenesis of and developing novel treatments for GCTB.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 1","pages":"20"},"PeriodicalIF":3.4,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142741088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"In Vitro differentiation of hair-follicle bulge stem cells into synaptophysin-expressing neurons: a potential new approach for neuro-regeneration.","authors":"Mohamad Mahjoor, Maliheh Nobakht, Fatemehsadat Ataei Kachouei, Hamidreza Zalpoor, Fatemeh Heidari, Abazar Yari, Sanaz Joulai Veijouye, Hojjatollah Nazari, Nayereh Sajedi","doi":"10.1007/s13577-024-01146-y","DOIUrl":"10.1007/s13577-024-01146-y","url":null,"abstract":"<p><p>Stem cells, particularly bulge hair follicle stem cells (HFSCs), have recently attracted significant interest due to their potential for tissue repair and regeneration. These cells, marked by their expression of Nestin (a neural stem cell marker), suggest the possibility of neural differentiation into neurons. This study investigated the use of retinoic acid (RA) and epidermal growth factor (EGF) to induce HFSC transformation into mature neurons, identified by synaptophysin expression. Rat whisker follicles were cultured in a medium suitable for HFSC survival and proliferation. Immunostaining techniques were used to identify HFSCs and assess their differentiation into neural cells. The addition of RA and EGF to the culture medium aimed to induce this differentiation. Findings demonstrate that HFSCs expressed Nestin, indicating their pluripotent nature. Treatment with RA and EGF resulted in synaptophysin expression, a marker of mature neurons, which was absent in the control group. However, this treatment group also displayed a decrease in the expression of other neural markers (βIII tubulin and NeuN). This study suggests that a combination of RA and EGF can accelerate HFSC differentiation into synaptophysin-positive cells in vitro. This research paves the way for further exploration of its potential application in neuro-regeneration.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 1","pages":"19"},"PeriodicalIF":3.4,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142640089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Human CellPub Date : 2024-11-13DOI: 10.1007/s13577-024-01147-x
Ningxin Ge, Kan Suzuki, Iori Sato, Michiya Noguchi, Yukio Nakamura, Mami Matsuo-Takasaki, Jun Fujishiro, Yohei Hayashi
{"title":"Generation of human induced pluripotent stem cell lines derived from patients of cystic biliary atresia.","authors":"Ningxin Ge, Kan Suzuki, Iori Sato, Michiya Noguchi, Yukio Nakamura, Mami Matsuo-Takasaki, Jun Fujishiro, Yohei Hayashi","doi":"10.1007/s13577-024-01147-x","DOIUrl":"10.1007/s13577-024-01147-x","url":null,"abstract":"<p><p>Biliary atresia (BA), resulting from abnormal development of the liver's internal or external bile ducts, can lead to liver damage and potentially fatal cirrhosis. Type I cystic biliary atresia is a relatively uncommon, but clinically significant variant of BA. It is critical to develop experimental models of BA to examine the etiology and pathogenesis, which remain elusive, and to develop future therapeutics. Here, we have successfully generated a panel of human induced pluripotent stem cells (hiPSCs) from five Japanese patients carrying type I cystic BA. These hiPSC lines exhibited characteristics of self-renewal and pluripotency. These cells held normal karyotypes mostly, but one of them carried hemizygous deletions, the clinical significance of which is unknown yet. Whole genome sequence analysis indicated that some of the mutations or single nucleotide polymorphisms (SNPs) commonly found in these patients are related to hepatobiliary abnormality. Given the limited understanding of the molecular pathogenesis of cystic BA, attributed to unknown factors of genetic and environmental causes, these cellular resources will be instrumental in replicating disease phenotypes and in advancing novel therapies for this disease.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 1","pages":"18"},"PeriodicalIF":3.4,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631013","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}
Human CellPub Date : 2024-11-12DOI: 10.1007/s13577-024-01144-0
Tao Wang, Lin Ye, Yingjie Zhou, Xionghan Zhang, Renjian Li, Yi Zhou, Jun Weng, Qingrong Mo, Yaqun Yu
{"title":"Pancreatic cancer-derived exosomal miR-510 promotes macrophage M2 polarization and facilitates cancer cell aggressive phenotypes.","authors":"Tao Wang, Lin Ye, Yingjie Zhou, Xionghan Zhang, Renjian Li, Yi Zhou, Jun Weng, Qingrong Mo, Yaqun Yu","doi":"10.1007/s13577-024-01144-0","DOIUrl":"10.1007/s13577-024-01144-0","url":null,"abstract":"<p><p>Extensive tumor microenvironment (TME) and tumor-associated macrophages (TAMs) contribute to the initiation and progression of pancreatic cancer (PC). Cancer cell-derived exosomal miRNAs that stimulate macrophage M2 polarization might play an important role in the process. In the current study, we observed significant upregulation of miR-510 in PC cell lines in comparison to normal HPDE cell line, with PANC-1 exhibiting the highest and MIA PaCa-2 the lowest miR-510 levels. Functional assays demonstrated that miR-510 overexpression enhanced, while its inhibition reduced, PC cell viability, migration, invasion, and EMT. In vivo, miR-510 mimics promoted tumor growth and macrophage M2 polarization, whereas miR-510 inhibition had the opposite effect. Exosomes from PANC-1 and MIA PaCa-2 cells, characterized by nanoparticle tracking analysis and TEM, contained significantly higher miR-510 levels than those from HPDE cells. Macrophages incubated with conditioned media from these PC cells showed increased M2 polarization markers, a process inhibited by the exosome inhibitor GW4869. The delivery of miR-510 via PC cell-derived exosomes facilitated macrophage M2 polarization and regulated the STAT signaling pathway, suggesting that exosomal miR-510 plays a crucial role in the tumor microenvironment of PC by modulating macrophage M2 polarization.</p>","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 1","pages":"17"},"PeriodicalIF":3.4,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142631020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}