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  1. Article: Derivation and validation of machine learning models for preoperative estimation of microvascular invasion risk in hepatocellular carcinoma.

    Chen, Zhiqiang / Zuo, Xueliang / Zhang, Yao / Han, Guoyong / Zhang, Long / Ding, Wenzhou / Wu, Jindao / Wang, Xuehao

    Annals of translational medicine

    2023  Volume 11, Issue 6, Page(s) 249

    Abstract: Background: Hepatocellular carcinoma (HCC) represents a considerable burden to patients and health systems. Microvascular invasion (MVI) is a significant risk factor for HCC recurrence and survival after hepatectomy. We aimed to establish a preoperative ...

    Abstract Background: Hepatocellular carcinoma (HCC) represents a considerable burden to patients and health systems. Microvascular invasion (MVI) is a significant risk factor for HCC recurrence and survival after hepatectomy. We aimed to establish a preoperative MVI prediction model based on readily available clinical and radiographic characteristics using machine learning algorithms.
    Methods: Two independent cohorts of patients with HCC who underwent hepatectomy were included in the analysis and divided into a derivation set (466 patients), an internal validation set (182 patients), and an external validation set (140 patients). Least absolute shrinkage and selection operator (LASSO) analysis was used to optimize variable selection. We constructed the MVI prediction model using several machine learning algorithms, including logistic regression, k-nearest neighbors, support vector machine, decision tree, random forest, extreme gradient boosting, and neural network. Performance of the model was assessed in terms of discrimination, calibration, and clinical usefulness.
    Results: The three most significant variables associated with MVI-α-fetoprotein, protein induced by vitamin K absence or antagonist-II, and tumor size-were identified by the LASSO analysis. Among the machine learning algorithms, the logistic regression model achieved the largest area under the receiver operating characteristic curve and was presented in the form of a user-friendly, online calculator. The concordance (C)-statistic of the model was 0.745 [95% confidence interval (CI): 0.701-0.790] for the derivation set, 0.771 (95% CI: 0.703-0.839) for the internal validation set, and 0.812 (95% CI: 0.734-0.891) for the external validation set. The Hosmer-Lemeshow calibration test and calibration plot indicated a good fit for all 3 data sets. Decision curve analysis showed the model was clinically useful.
    Conclusions: This study provided a convenient and explainable approach for MVI prediction before surgical intervention. Our model may assist clinicians in determining the optimal therapeutic modality and facilitate precision medicine for HCC.
    Language English
    Publishing date 2023-01-06
    Publishing country China
    Document type Journal Article
    ZDB-ID 2893931-1
    ISSN 2305-5847 ; 2305-5839
    ISSN (online) 2305-5847
    ISSN 2305-5839
    DOI 10.21037/atm-22-2828
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: M2 macrophage-secreted exosomes promote metastasis and increase vascular permeability in hepatocellular carcinoma.

    Lu, Yiwei / Han, Guoyong / Zhang, Yao / Zhang, Long / Li, Zhi / Wang, Qingyuan / Chen, Zhiqiang / Wang, Xuehao / Wu, Jindao

    Cell communication and signaling : CCS

    2023  Volume 21, Issue 1, Page(s) 299

    Abstract: Background: Metastasis is a key feature of malignant tumors and significantly contributes to their high mortality, particularly in hepatocellular carcinoma (HCC). Therefore, it is imperative to explore the mechanism of tumor metastasis. Recently, tumor- ... ...

    Abstract Background: Metastasis is a key feature of malignant tumors and significantly contributes to their high mortality, particularly in hepatocellular carcinoma (HCC). Therefore, it is imperative to explore the mechanism of tumor metastasis. Recently, tumor-associated macrophages (TAMs) have been demonstrated to promote tumor progression, while TAM-derived molecules involved in HCC metastasis warrant further investigation.
    Methods: THP-1 was treated with IL-4 (Interleukin-4) and IL-13 (Interleukin-13) for M2 polarized macrophages. Exosomes derived from M2 macrophages were characterized. Then, HCC cells or human umbilical vein endothelial cells (HUVECs) were co-cultured with M2 macrophages or treated with M2 macrophage-secreted exosomes. Next, Transwell®, Scratch assay, tube formation, and endothelial permeability assays were performed. Moreover, RT-PCR, western blotting, immunofluorescence, and ELISA were used to assess mRNA and protein expression levels. Finally, the miRNA expression profiles of exosomes derived from M2 and M0 macrophages were analyzed.
    Results: M2 macrophage infiltration was correlated with metastasis and a poor prognosis in HCC patients. M2-derived exosomes were absorbed by HCC and HUVEC cells and promoted the epithelial-mesenchymal transition (EMT), vascular permeability, and angiogenesis. Notably, MiR-23a-3p levels were significantly higher in M2-derived exosomes and hnRNPA1 mediated miR-23a-3p packaging into exosomes. Phosphatase and tensin homolog (PTEN) and tight junction protein 1 (TJP1) were the targets of miR-23a-3p, as confirmed by luciferase reporter assays. Lastly, HCC cells co-cultured with M2-derived exosomes secreted more GM-CSF, VEGF, G-CSF, MCP-1, and IL-4, which in turn further recruited M2 macrophages.
    Conclusions: Our findings suggest that M2 macrophage-derived miR-23a-3p enhances HCC metastasis by promoting EMT and angiogenesis, as well as increasing vascular permeability. Video Abstract.
    MeSH term(s) Humans ; Carcinoma, Hepatocellular/pathology ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Interleukin-4 ; Liver Neoplasms/pathology ; Capillary Permeability ; Exosomes/metabolism ; Endothelial Cells/metabolism ; Cell Line, Tumor ; Macrophages/metabolism
    Chemical Substances MicroRNAs ; Interleukin-4 (207137-56-2)
    Language English
    Publishing date 2023-10-30
    Publishing country England
    Document type Video-Audio Media ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2126315-2
    ISSN 1478-811X ; 1478-811X
    ISSN (online) 1478-811X
    ISSN 1478-811X
    DOI 10.1186/s12964-022-00872-w
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Nuclear delivery of dual anti-cancer drugs by molecular self-assembly

    Wu, Jindao / Ding, Wenzhou / Han, Guoyong / You, Wei / Gao, Wen / Shen, Hongbing / Tang, Jinhai / Tang, Qiyun / Wang, Xuehao

    Biomaterials science. 2021 Jan. 5, v. 9, no. 1

    2021  

    Abstract: Nanomedicines generally suffer from poor accumulation in tumor cells, low anti-tumor efficacy, and drug resistance. In order to address these problems, we introduced a novel nanomedicine based on dual anti-cancer drugs, which showed good cell nuclear ... ...

    Abstract Nanomedicines generally suffer from poor accumulation in tumor cells, low anti-tumor efficacy, and drug resistance. In order to address these problems, we introduced a novel nanomedicine based on dual anti-cancer drugs, which showed good cell nuclear accumulation properties. The novel nanomedicine consisted of three components: (1) dual anti-cancer drugs, 10-hydroxycamptothecin (HCPT) and chlorambucil (CRB), whose targets are located in the cell nucleus, (2) a nuclear localizing dodecapeptide, PMI peptide (TSFAEYWNLLSP), which could activate p53 by binding with MDM2 and MDMX located in the cell nucleus, and (3) an efficient self-assembling tripeptide FFY. Our nanomedicine exhibited enhanced cellular uptake and nuclear accumulation properties, thus achieving an excellent anti-cancer capacity both in vitro and in vivo. Our study will provide an inspiration for the development of novel multifunctional nanomaterials for cancer diagnosis and therapy.
    Keywords biocompatible materials ; cell nucleus ; drug resistance ; nanomedicine ; neoplasms ; therapeutics ; tripeptides
    Language English
    Dates of publication 2021-0105
    Size p. 116-123.
    Publishing place The Royal Society of Chemistry
    Document type Article
    Note NAL-AP-2-clean
    ZDB-ID 2693928-9
    ISSN 2047-4849 ; 2047-4830
    ISSN (online) 2047-4849
    ISSN 2047-4830
    DOI 10.1039/d0bm00971g
    Database NAL-Catalogue (AGRICOLA)

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  4. Article: CircRHBDD1 augments metabolic rewiring and restricts immunotherapy efficacy via m

    Cai, Juan / Chen, Zhiqiang / Zhang, Yao / Wang, Jinguo / Zhang, Zhengrong / Wu, Jindao / Mao, Jiading / Zuo, Xueliang

    Molecular therapy oncolytics

    2022  Volume 24, Page(s) 755–771

    Abstract: Circular RNAs are a class of highly conserved RNAs with stable covalently closed circular structures. Metabolic reprogramming of cancer cells reshapes the tumor microenvironment and can suppress antitumor immunity. Here, we discovered a novel circular ... ...

    Abstract Circular RNAs are a class of highly conserved RNAs with stable covalently closed circular structures. Metabolic reprogramming of cancer cells reshapes the tumor microenvironment and can suppress antitumor immunity. Here, we discovered a novel circular RNA, termed circRHBDD1, which augments aerobic glycolysis and restricts anti-PD-1 therapy in hepatocellular carcinoma (HCC). Mechanistic studies revealed that circRHBDD1 recruits the m
    Language English
    Publishing date 2022-02-22
    Publishing country United States
    Document type Journal Article
    ISSN 2372-7705
    ISSN 2372-7705
    DOI 10.1016/j.omto.2022.02.021
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: E2F1-mediated GINS2 transcriptional activation promotes tumor progression through PI3K/AKT/mTOR pathway in hepatocellular carcinoma.

    Zhang, Yao / Hao, Xiaopei / Han, Guoyong / Lu, Yiwei / Chen, Zhiqiang / Zhang, Long / Wu, Jindao / Wang, Xuehao

    American journal of cancer research

    2022  Volume 12, Issue 4, Page(s) 1707–1726

    Abstract: Hepatocellular carcinoma (HCC) has high morbidity and mortality rates. It is therefore imperative to study the underlying mechanism of HCC to identify potential prognostic biomarkers and therapeutic targets. Recently, GINS2 has been identified to be a ... ...

    Abstract Hepatocellular carcinoma (HCC) has high morbidity and mortality rates. It is therefore imperative to study the underlying mechanism of HCC to identify potential prognostic biomarkers and therapeutic targets. Recently, GINS2 has been identified to be a cancer-promoting gene in different cancer types. Nevertheless, the exact mechanism of GINS2 in HCC remains to be elucidated. To systematically explore the significance of GINS2, we first assessed the relative expression of GINS2 in pan-cancers based on data obtained from the HCCDB, TIMER, and TCGA databases. Then, we explored the clinical significance of GINS2 in HCC through Kaplan-Meier method as well as univariate and multivariate cox regression analysis. Additionally, functional enrichment analysis of GINS2 was done through GO, KEGG, PPI network, and immune cell infiltration analyses. Functional experiments were also conducted to investigate the biological significance of GINS2 in HCC cell lines. Our research revealed that GINS2 is involved in HCC progression and highlighted its potential value as a crucial diagnostic and therapeutic target for HCC.
    Language English
    Publishing date 2022-04-15
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2589522-9
    ISSN 2156-6976
    ISSN 2156-6976
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Hypoxia-associated circPRDM4 promotes immune escape via HIF-1α regulation of PD-L1 in hepatocellular carcinoma.

    Chen, Zhi-Qiang / Zuo, Xue-Liang / Cai, Juan / Zhang, Yao / Han, Guo-Yong / Zhang, Long / Ding, Wen-Zhou / Wu, Jin-Dao / Wang, Xue-Hao

    Experimental hematology & oncology

    2023  Volume 12, Issue 1, Page(s) 17

    Abstract: Background: Hypoxia is a hallmark of cancer, and is closely intertwined with tumor immune evasion. Circular RNAs (circRNAs) have been implicated in tumor response to immune checkpoint blockades. However, hypoxia-associated circRNAs that orchestrate the ... ...

    Abstract Background: Hypoxia is a hallmark of cancer, and is closely intertwined with tumor immune evasion. Circular RNAs (circRNAs) have been implicated in tumor response to immune checkpoint blockades. However, hypoxia-associated circRNAs that orchestrate the association between hypoxia and response to immunotherapy remain poorly understood. Here, we aimed to determine the roles of hypoxia-associated circRNAs in immune escape of hepatocellular carcinoma (HCC) cells.
    Methods: Differentially expressed hypoxia-associated circRNAs were determined using high-throughput sequencing technology. HCC patients treated with PD-1 blockade were enrolled to assess the clinical significance of circPRDM4. RT-qPCR, western blotting, flow cytometry, T cell-mediated tumor cell killing assay, and enzyme linked immunosorbent assay were used to investigate the roles of circPRDM4 in immune escape of HCC cells in vitro. Patient-derived xenograft mouse models and adoptive human tumor infiltrating lymphocyte-CD8
    Results: We identified circPRDM4 as a hypoxia-associated circRNA in HCC. circPRDM4 was upregulated in responders to PD-1 blockade and associated with therapeutic efficacy. In vitro and in vivo experiments showed that circPRDM4 induced PD-L1 expression and promoted CD8
    Conclusions: These findings illustrated that circPRDM4 promoted immune escape of HCC cells by facilitating the recruitment of HIF-1α onto the promoter of CD274 under hypoxia, thereby inhibiting CD8
    Language English
    Publishing date 2023-02-06
    Publishing country England
    Document type Journal Article
    ZDB-ID 2669066-4
    ISSN 2162-3619
    ISSN 2162-3619
    DOI 10.1186/s40164-023-00378-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: STK39 enhances the progression of Cholangiocarcinoma via PI3K/AKT pathway.

    Hao, Xiaopei / Zhang, Yao / Lu, Yiwei / Han, Guoyong / Rong, Dawei / Sun, Guoqiang / Sun, Guangshun / Tang, Weiwei / Wu, Jindao / Wang, Xuehao

    iScience

    2021  Volume 24, Issue 11, Page(s) 103223

    Abstract: Serine/threonine kinase 39 (STK39) is overexpressed in various tumor tissues and plays an essential role in tumor progression. In this study, we investigated the clinical value, as well as the potential functions and mechanisms of STK39 in ... ...

    Abstract Serine/threonine kinase 39 (STK39) is overexpressed in various tumor tissues and plays an essential role in tumor progression. In this study, we investigated the clinical value, as well as the potential functions and mechanisms of STK39 in cholangiocarcinoma (CCA). The results showed that STK39 was overexpressed in CCA and negatively associated with the prognosis of patients with CCA. Functionally, STK39 knockdown suppressed cell proliferation, migration, and invasion, while STK39 overexpression facilitated tumor aggressiveness. The tumor-promoting effects of STK39 in CCA were also validated by
    Language English
    Publishing date 2021-10-06
    Publishing country United States
    Document type Journal Article
    ISSN 2589-0042
    ISSN (online) 2589-0042
    DOI 10.1016/j.isci.2021.103223
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Nuclear delivery of dual anti-cancer drugs by molecular self-assembly.

    Wu, Jindao / Ding, Wenzhou / Han, Guoyong / You, Wei / Gao, Wen / Shen, Hongbing / Tang, Jinhai / Tang, Qiyun / Wang, Xuehao

    Biomaterials science

    2020  Volume 9, Issue 1, Page(s) 116–123

    Abstract: Nanomedicines generally suffer from poor accumulation in tumor cells, low anti-tumor efficacy, and drug resistance. In order to address these problems, we introduced a novel nanomedicine based on dual anti-cancer drugs, which showed good cell nuclear ... ...

    Abstract Nanomedicines generally suffer from poor accumulation in tumor cells, low anti-tumor efficacy, and drug resistance. In order to address these problems, we introduced a novel nanomedicine based on dual anti-cancer drugs, which showed good cell nuclear accumulation properties. The novel nanomedicine consisted of three components: (1) dual anti-cancer drugs, 10-hydroxycamptothecin (HCPT) and chlorambucil (CRB), whose targets are located in the cell nucleus, (2) a nuclear localizing dodecapeptide, PMI peptide (TSFAEYWNLLSP), which could activate p53 by binding with MDM2 and MDMX located in the cell nucleus, and (3) an efficient self-assembling tripeptide FFY. Our nanomedicine exhibited enhanced cellular uptake and nuclear accumulation properties, thus achieving an excellent anti-cancer capacity both in vitro and in vivo. Our study will provide an inspiration for the development of novel multifunctional nanomaterials for cancer diagnosis and therapy.
    MeSH term(s) Antineoplastic Agents ; Cell Line, Tumor ; Humans ; Nanomedicine ; Neoplasms/drug therapy ; Tumor Suppressor Protein p53
    Chemical Substances Antineoplastic Agents ; Tumor Suppressor Protein p53
    Language English
    Publishing date 2020-12-16
    Publishing country England
    Document type Journal Article
    ZDB-ID 2693928-9
    ISSN 2047-4849 ; 2047-4830
    ISSN (online) 2047-4849
    ISSN 2047-4830
    DOI 10.1039/d0bm00971g
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: M6A-mediated upregulation of LINC00958 increases lipogenesis and acts as a nanotherapeutic target in hepatocellular carcinoma.

    Zuo, Xueliang / Chen, Zhiqiang / Gao, Wen / Zhang, Yao / Wang, Jinguo / Wang, Junfeng / Cao, Ming / Cai, Juan / Wu, Jindao / Wang, Xuehao

    Journal of hematology & oncology

    2020  Volume 13, Issue 1, Page(s) 5

    Abstract: Background: Long non-coding RNAs (lncRNAs) possess significant regulatory functions in multiple biological and pathological processes, especially in cancer. Dysregulated lncRNAs in hepatocellular carcinoma (HCC) and their therapeutic applications remain ...

    Abstract Background: Long non-coding RNAs (lncRNAs) possess significant regulatory functions in multiple biological and pathological processes, especially in cancer. Dysregulated lncRNAs in hepatocellular carcinoma (HCC) and their therapeutic applications remain unclear.
    Methods: Differentially expressed lncRNA profile in HCC was constructed using TCGA data. LINC00958 expression level was examined in HCC cell lines and tissues. Univariate and multivariate analyses were performed to demonstrate the prognostic value of LINC00958. Loss-of-function and gain-of-function experiments were used to assess the effects of LINC00958 on cell proliferation, motility, and lipogenesis. Patient-derived xenograft model was established for in vivo experiments. RNA immunoprecipitation, dual luciferase reporter, biotin-labeled miRNA pull-down, fluorescence in situ hybridization, and RNA sequencing assays were performed to elucidate the underlying molecular mechanisms. We developed a PLGA-based nanoplatform encapsulating LINC00958 siRNA and evaluated its superiority for systemic administration.
    Results: We identified a lipogenesis-related lncRNA, LINC00958, whose expression was upregulated in HCC cell lines and tissues. High LINC00958 level independently predicted poor overall survival. Functional assays showed that LINC00958 aggravated HCC malignant phenotypes in vitro and in vivo. Mechanistically, LINC00958 sponged miR-3619-5p to upregulate hepatoma-derived growth factor (HDGF) expression, thereby facilitating HCC lipogenesis and progression. METTL3-mediated N
    Conclusions: Our results delineate the clinical significance of LINC00958 in HCC and the regulatory mechanisms involved in HCC lipogenesis and progression, providing a novel prognostic indicator and promising nanotherapeutic target.
    MeSH term(s) Adenosine/analogs & derivatives ; Adenosine/metabolism ; Animals ; Carcinoma, Hepatocellular/genetics ; Carcinoma, Hepatocellular/metabolism ; Carcinoma, Hepatocellular/pathology ; Carcinoma, Hepatocellular/therapy ; Cell Line, Tumor ; Disease Progression ; Gene Expression Regulation, Neoplastic ; Genetic Therapy ; Humans ; Lipogenesis ; Liver Neoplasms/genetics ; Liver Neoplasms/metabolism ; Liver Neoplasms/pathology ; Liver Neoplasms/therapy ; Mice, Inbred BALB C ; Mice, SCID ; RNA, Long Noncoding/genetics ; Up-Regulation
    Chemical Substances RNA, Long Noncoding ; N-methyladenosine (CLE6G00625) ; Adenosine (K72T3FS567)
    Language English
    Publishing date 2020-01-08
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2429631-4
    ISSN 1756-8722 ; 1756-8722
    ISSN (online) 1756-8722
    ISSN 1756-8722
    DOI 10.1186/s13045-019-0839-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: MiR-3174 promotes proliferation and inhibits apoptosis by targeting FOXO1 in hepatocellular carcinoma.

    Wang, Qingyuan / Yang, Xiao / Zhou, Xiao / Wu, Bin / Zhu, Deming / Jia, Wenbo / Chu, Jian / Wang, Jinyi / Wu, Jindao / Kong, Lianbao

    Biochemical and biophysical research communications

    2020  Volume 526, Issue 4, Page(s) 889–897

    Abstract: Introduction: MicroRNAs (miRNAs) have been confirmed to play a crucial part in oncogenesis. Several studies suggested that MiR-3174 act as a tumor promoter in various Malignant neoplasm. However, the biological function of miR-3174 in hepatocellular ... ...

    Abstract Introduction: MicroRNAs (miRNAs) have been confirmed to play a crucial part in oncogenesis. Several studies suggested that MiR-3174 act as a tumor promoter in various Malignant neoplasm. However, the biological function of miR-3174 in hepatocellular carcinoma (HCC) still highly unexplored.
    Methods: We screened differentially over-expressed miRNAs by The Cancer Genome Atlas (TCGA) and the GEO databases. The expression of miR-3174 in HCC cells and tissues was detected by qRT-PCR. The cellular behaviors of transfected cells were respectively examined by colony formation assays, EdU Assays and flow cytometry. Forkhead box O1 transcription factor (FOXO1) was predicted and confirmed as a direct target of miR-3174 by bioinformatics analysis and dual-luciferase reporter gene assay.
    Results: MiR-3174 was up-regulated in HCC tissues and cells, and the expression level of it was highly associated with tumor size and Edmondson grade. Our study pioneering validates that upregulated miR-3174 promote cell proliferation and inhibit cell apoptosis in vitro and in vivo. Meanwhile, our study verified that miR-3174 regulate Bim, P21, cyclin D1 and c-MYC expression by directly targeting FOXO1.
    Conclusion: The upregulated miR-3174 promote cell proliferation and inhibit cell apoptosis by downregulating FOXO1 expression in HCC. MiR-3174 may be a novel candidate for targeted delivery of miRNA therapeutics for HCC patients.
    MeSH term(s) 3' Untranslated Regions/genetics ; Animals ; Antineoplastic Agents/metabolism ; Apoptosis/genetics ; Carcinogenesis/genetics ; Carcinogenesis/pathology ; Carcinoma, Hepatocellular/genetics ; Carcinoma, Hepatocellular/pathology ; Cell Line, Tumor ; Cell Proliferation/genetics ; Female ; Forkhead Box Protein O1/genetics ; Forkhead Box Protein O1/metabolism ; Gene Deletion ; Gene Expression Regulation, Neoplastic ; Humans ; Liver Neoplasms/genetics ; Liver Neoplasms/pathology ; Male ; Mice, Inbred BALB C ; Mice, Nude ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Middle Aged ; Protein Binding/genetics ; Up-Regulation/genetics ; Xenograft Model Antitumor Assays
    Chemical Substances 3' Untranslated Regions ; Antineoplastic Agents ; FOXO1 protein, human ; Forkhead Box Protein O1 ; MicroRNAs
    Language English
    Publishing date 2020-04-10
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 205723-2
    ISSN 1090-2104 ; 0006-291X ; 0006-291X
    ISSN (online) 1090-2104 ; 0006-291X
    ISSN 0006-291X
    DOI 10.1016/j.bbrc.2020.03.152
    Database MEDical Literature Analysis and Retrieval System OnLINE

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