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  • 1
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    Online Resource
    The inhibitory effect of silencing CDCA3 on migration and proliferation in bladder urothelial carcinoma
    Springer Science and Business Media LLC ; 2021
    In:  Cancer Cell International Vol. 21, No. 1 ( 2021-12)
    Details
    In: Cancer Cell International, Springer Science and Business Media LLC, Vol. 21, No. 1 ( 2021-12)
    Abstract: CDCA3 is an important component of the E3 ligase complex with SKP1 and CUL1, which could regulate the progress of cell mitosis. CDCA3 has been widely identified as a proto-oncogene in multiple human cancers, however, its role in promoting human bladder urothelial carcinoma has not been fully elucidated. Methods Bioinformatic methods were used to analyze the expression level of CDCA3 in human bladder urothelial carcinoma tissues and the relationship between its expression level and key clinical characteristics. In vitro studies were performed to validate the specific functions of CDCA3 in regulating cell proliferation, cell migration and cell cycle process. Alterations of related proteins was investigated by western blot assays. In vivo studies were constructed to validate whether silencing CDCA3 could inhibit the proliferation rate in mice model. Results Bioinformatic analysis revealed that CDCA3 was significantly up-regulated in bladder urothelial carcinoma samples and was related to key clinical characteristics, such as tumor grade and metastasis. Moreover, patients who had higher expression level of CDCA3 tend to show a shorter life span. In vitro studies revealed that silencing CDCA3 could impair the migration ability of tumor cells via down-regulating EMT-related proteins such as MMP9 and Vimentin and inhibit tumor cell growth via arresting cells in the G1 cell cycle phase through regulating cell cycle related proteins like p21. In vivo study confirmed that silencing CDCA3 could inhibit the proliferation of bladder urothelial carcinoma cells. Conclusions CDCA3 is an important oncogene that could strengthen the migration ability of bladder urothelial carcinoma cells and accelerate tumor cell growth via regulating cell cycle progress and is a potential biomarker of bladder urothelial carcinoma.
    Type of Medium: Online Resource
    ISSN: 1475-2867
    URL: Article
    DOI: 10.1186/s12935-021-01969-x
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2091573-1
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  • 2
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    Image_1.pdf
    Frontiers Media SA ; 2021
    In:  Frontiers in Oncology Vol. 10 ( 2021-2-8)
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    In: Frontiers in Oncology, Frontiers Media SA, Vol. 10 ( 2021-2-8)
    Abstract: Kidney renal clear cell carcinoma (KIRC) and kidney renal papillary cell carcinoma (KIRP) are the most common RCC types. RCC has high immune infiltration levels, and immunotherapy is currently one of the most promising treatments for RCC. Collagen triple helix repeat containing 1 (CTHRC1) is an extracellular matrix protein that regulates tumor invasion and modulates the tumor microenvironment. However, the association of CTHRC1 with the prognosis and tumor-infiltrating lymphocytes of KIRP and KIRC has not been reported. We examined the CTHRC1 expression differences in multiple tumor tissues and normal tissues via exploring TIMER, Oncomine, and UALCAN databases. Then, we searched the Kaplan-Meier plotter database to evaluate the correlation of CTHRC1 mRNA level with clinical outcomes. Subsequently, the TIMER platform and TISIDB website were chosen to assess the correlation of CTHRC1 with tumor immune cell infiltration level. We further explored the causes of aberrant CTHRC1 expression in tumorigenesis. We found that CTHRC1 level was significantly elevated in KIRP and KIRC tissues relative to normal tissues. CTHRC1 expression associates with tumor stage, histology, lymph node metastasis, and poor clinical prognosis in KIRP. The CTHRC1 level correlates to tumor grade, stage, nodal metastasis, and worse survival prognosis. Additionally, CTHRC1 is positively related to different tumor-infiltrating immune cells in KIRP and KIRC. Moreover, CTHRC1 was closely correlated with the gene markers of diverse immune cells. Also, high CTHRC1 expression predicted a worse prognosis in KIRP and KIRC based on immune cells. Copy number variations (CNV) and DNA methylation might contribute to the abnormal upregulation of CTHRC1 in KIRP and KIRC. In conclusion, CTHRC1 can serve as a biomarker to predict the prognosis and immune infiltration in KIRP and KIRC.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    URL: Article
    DOI: 10.3389/fonc.2020.570819
    DOI: 10.3389/fonc.2020.570819.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2649216-7
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  • 3
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    E3 ubiquitin ligase RNF126 affects bladder cancer progression through regulation of PTEN stability
    Springer Science and Business Media LLC ; 2021
    In:  Cell Death & Disease Vol. 12, No. 3 ( 2021-03-04)
    Details
    In: Cell Death & Disease, Springer Science and Business Media LLC, Vol. 12, No. 3 ( 2021-03-04)
    Abstract: E3 ubiquitin ligase RNF126 (ring finger protein 126) is highly expressed in various cancers and strongly associated with tumorigenesis. However, its specific function in bladder cancer (BCa) is still debatable. Here, we found that RNF126 was significantly upregulated in BCa tissue by TCGA database, and our studies indicated that downregulation of RNF126 significantly inhibited cell proliferation and metastasis through the EGFR/PI3K/AKT signaling pathway in BCa cells. Furthermore, we identified PTEN, an inhibitor of the PI3K/AKT signaling pathway, as a novel substrate for RNF126. By co-immunoprecipitation assays, we proved that RNF126 directly interacts with PTEN. Predominantly, PTEN binds to the C-terminal containing the RING domain of RNF126. The in vivo ubiquitination assay showed that RNF126 specifically regulates PTEN stability through poly-ubiquitination. Furthermore, PTEN knockdown restored cell proliferation, metastasis, and tumor formation of BCa cells inhibited by RNF126 silencing in vitro and in vivo. In conclusion, these results identified RNF126 as an oncogene that functions through ubiquitination and degradation of PTEN in BCa.
    Type of Medium: Online Resource
    ISSN: 2041-4889
    URL: Article
    DOI: 10.1038/s41419-021-03521-1
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
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  • 4
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    Online Resource
    Ultrasensitive tumour‐agnostic non‐invasive detection of colorectal cancer recurrence using ctDNA methylation
    Wiley ; 2022
    In:  Clinical and Translational Medicine Vol. 12, No. 9 ( 2022-09)
    Details
    In: Clinical and Translational Medicine, Wiley, Vol. 12, No. 9 ( 2022-09)
    Type of Medium: Online Resource
    ISSN: 2001-1326 , 2001-1326
    URL: Issue
    URL: Article
    DOI: 10.1002/ctm2.v12.9
    DOI: 10.1002/ctm2.1015
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2697013-2
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  • 5
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    PRR11 promotes ccRCC tumorigenesis by regulating E2F1 stability
    American Society for Clinical Investigation ; 2021
    In:  JCI Insight Vol. 6, No. 19 ( 2021-10-8)
    Details
    In: JCI Insight, American Society for Clinical Investigation, Vol. 6, No. 19 ( 2021-10-8)
    Type of Medium: Online Resource
    ISSN: 2379-3708
    URL: Article
    URL: Article
    DOI: 10.1172/jci.insight.145172
    DOI: 10.1172/jci.insight.145172DS1
    Language: English
    Publisher: American Society for Clinical Investigation
    Publication Date: 2021
    detail.hit.zdb_id: 2874757-4
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  • 6
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    The impact of preanalytical variables on the analysis of cell-free DNA from blood and urine samples
    Frontiers Media SA ; 2024
    In:  Frontiers in Cell and Developmental Biology Vol. 12 ( 2024-5-9)
    Details
    In: Frontiers in Cell and Developmental Biology, Frontiers Media SA, Vol. 12 ( 2024-5-9)
    Abstract: Cell-free DNA (cfDNA), a burgeoning class of molecular biomarkers, has been extensively studied across a variety of biomedical fields. As a key component of liquid biopsy, cfDNA testing is gaining prominence in disease detection and management due to the convenience of sample collection and the abundant wealth of genetic information it provides. However, the broader clinical application of cfDNA is currently impeded by a lack of standardization in the preanalytical procedures for cfDNA analysis. A number of fundamental challenges, including the selection of appropriate preanalytical procedures, prevention of short cfDNA fragment loss, and the validation of various cfDNA measurement methods, remain unaddressed. These existing hurdles lead to difficulties in comparing results and ensuring repeatability, thereby undermining the reliability of cfDNA analysis in clinical settings. This review discusses the crucial preanalytical factors that influence cfDNA analysis outcomes, including sample collection, transportation, temporary storage, processing, extraction, quality control, and long-term storage. The review provides clarification on achievable consensus and offers an analysis of the current issues with the goal of standardizing preanalytical procedures for cfDNA analysis.
    Type of Medium: Online Resource
    ISSN: 2296-634X
    URL: Article
    DOI: 10.3389/fcell.2024.1385041
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2024
    detail.hit.zdb_id: 2737824-X
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  • 7
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    The inhibitory effect of melatonin on human prostate cancer
    Springer Science and Business Media LLC ; 2021
    In:  Cell Communication and Signaling Vol. 19, No. 1 ( 2021-03-15)
    Details
    In: Cell Communication and Signaling, Springer Science and Business Media LLC, Vol. 19, No. 1 ( 2021-03-15)
    Abstract: Prostate cancer (PCa) is one of the most commonly diagnosed human cancers in males. Nearly 191,930 new cases and 33,330 new deaths of PCa are estimated in 2020. Androgen and androgen receptor pathways played essential roles in the pathogenesis of PCa. Androgen depletion therapy is the most used therapies for primary PCa patients. However, due to the high relapse and mortality of PCa, developing novel noninvasive therapies have become the focus of research. Melatonin is an indole-like neurohormone mainly produced in the human pineal gland with a prominent anti-oxidant property. The anti-tumor ability of melatonin has been substantially confirmed and several related articles have also reported the inhibitory effect of melatonin on PCa, while reviews of this inhibitory effect of melatonin on PCa in recent 10 years are absent. Therefore, we systematically discuss the relationship between melatonin disruption and the risk of PCa, the mechanism of how melatonin inhibited PCa, and the synergistic benefits of melatonin and other drugs to summarize current understandings about the function of melatonin in suppressing human prostate cancer. We also raise several unsolved issues that need to be resolved to translate currently non-clinical trials of melatonin for clinic use. We hope this literature review could provide a solid theoretical basis for the future utilization of melatonin in preventing, diagnosing and treating human prostate cancer.
    Type of Medium: Online Resource
    ISSN: 1478-811X
    URL: Article
    URL: Article
    DOI: 10.1186/s12964-021-00723-0
    DOI: 10.21203/rs.3.rs-969955/v1
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2126315-2
    SSG: 12
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  • 8
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    Suppressive effects of plumbagin on the growth of human bladder cancer cells via PI3K/AKT/mTOR signaling pathways and EMT
    Springer Science and Business Media LLC ; 2020
    In:  Cancer Cell International Vol. 20, No. 1 ( 2020-12)
    Details
    In: Cancer Cell International, Springer Science and Business Media LLC, Vol. 20, No. 1 ( 2020-12)
    Abstract: Novel chemotherapeutic drugs with good anti-tumor activity are of pressing need for bladder cancer treatment. In this study, plumbagin (PL), a natural plant-derived drug extracted from Chinese herbals, was identified as a promising candidate for human bladder cancer (BCa) chemotherapy. Methods The anti-tumor activity of PL was evaluated using a series of in vitro experiments, such as MTT, transwell assay, flow cytometry, quantitative real-time PCR (qRT-PCR) and western blotting. We established xenograft tumors in nude mice by subcutaneous injection with the human bladder cancer T24 cells. Results The results showed that PL could inhibit the proliferation, migration and survival of BCa cells (T24 and UMUC3 cells) in a time- and dose-dependent way. We found PL promotes the cell cycle arrest and apoptosis by inhibiting PI3K/AKT/mTOR signaling pathway, which inhibits cell proliferation. In vivo, anti-tumor activity of PL was further investigated using a BCa cell xenograft mice model. To simulate clinical chemotherapy, the PL were intravenously injected with a dose of 10 mg/kg for 10 times. Compared with the blank control, the tumor weight in PL treated group decreased significantly from 0.57 ± 0.04 g to 0.21 ± 0.06 g ( P   〈  0.001). Conclusions In our study. We found PL inhibits the proliferation of T24 and UMUC3 cells in vivo and in vitro, which may play a role through several downstream effectors of PI3K/AKT/mTOR signaling pathway to promote the cell cycle arrest and apoptosis. Meanwhile, we consider that PL may inhibit the migration of bladder cancer cells via EMT suppression and induce ROS generation to make cell apoptosis. This work screened out a novel chemotherapeutic drug (plumbagin) with relatively good anti-tumor activity, which possessed great potential in BCa chemotherapy.
    Type of Medium: Online Resource
    ISSN: 1475-2867
    URL: Article
    DOI: 10.1186/s12935-020-01607-y
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2091573-1
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  • 9
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    Online Resource
    Melatonin inhibits bladder tumorigenesis by suppressing PPARγ/ENO1-mediated glycolysis
    Springer Science and Business Media LLC ; 2023
    In:  Cell Death & Disease Vol. 14, No. 4 ( 2023-04-06)
    Details
    In: Cell Death & Disease, Springer Science and Business Media LLC, Vol. 14, No. 4 ( 2023-04-06)
    Abstract: Melatonin is a well-known natural hormone, which shows a potential anticancer effect in many human cancers. Bladder cancer (BLCA) is one of the most malignant human cancers in the world. Chemoresistance is an increasingly prominent phenomenon that presents an obstacle to the clinical treatment of BLCA. There is an urgent need to investigate novel drugs to improve the current clinical status. In our study, we comprehensively explored the inhibitory effect of melatonin on BLCA and found that it could suppress glycolysis process. Moreover, we discovered that ENO1, a glycolytic enzyme involved in the ninth step of glycolysis, was the downstream effector of melatonin and could be a predictive biomarker of BLCA. We also proved that enhanced glycolysis simulated by adding exogenous pyruvate could induce gemcitabine resistance, and melatonin treatment or silencing of ENO1 could intensify the cytotoxic effect of gemcitabine on BLCA cells. Excessive accumulation of reactive oxygen species (ROS) mediated the inhibitory effect of melatonin on BLCA cells. Additionally, we uncovered that PPARγ was a novel upstream regulator of ENO1, which mediated the downregulation of ENO1 caused by melatonin. Our study offers a fresh perspective on the anticancer effect of melatonin and encourages further studies on clinical chemoresistance.
    Type of Medium: Online Resource
    ISSN: 2041-4889
    URL: Article
    DOI: 10.1038/s41419-023-05770-8
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
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  • 10
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    Non‐invasive diagnosis and surveillance of bladder cancer with driver and passenger DNA methylation in a prospective cohort study
    Wiley ; 2022
    In:  Clinical and Translational Medicine Vol. 12, No. 8 ( 2022-08)
    Details
    In: Clinical and Translational Medicine, Wiley, Vol. 12, No. 8 ( 2022-08)
    Abstract: State‐of‐art non‐invasive diagnosis processes for bladder cancer (BLCA) harbour shortcomings such as low sensitivity and specificity, unable to distinguish between high‐ (HG) and low‐grade (LG) tumours, as well as inability to differentiate muscle‐invasive bladder cancer (MIBC) and non‐muscle‐invasive bladder cancer (NMIBC). This study investigates a comprehensive characterization of the entire DNA methylation (DNAm) landscape of BLCA to determine the relevant biomarkers for the non‐invasive diagnosis of BLCA. Methods A total of 304 samples from 224 donors were enrolled in this multi‐centre, prospective cohort study. BLCA‐specific DNAm signature discovery was carried out with genome‐wide bisulfite sequencing in 32 tumour tissues and 12 normal urine samples. A targeted sequencing assay for BLCA‐specific DNAm signatures was developed to categorize tumour tissue against normal urine, or MIBC against NMIBC. Independent validation was performed with targeted sequencing of 259 urine samples in a double‐blinded manner to determine the clinical diagnosis and prognosis value of DNAm‐based classification models. Functions of genomic region harbouring BLCA‐specific DNAm signature were validated with biological assays. Concordances of pathology to urine tumour DNA (circulating tumour DNA [ctDNA]) methylation, genomic mutations or other state‐of‐the‐art diagnosis methods were measured. Results Genome‐wide DNAm profile could accurately classify LG tumour from HG tumour (LG NMIBC vs. HG NMIBC: p  = .038; LG NMIBC vs. HG MIBC, p  = .00032; HG NMIBC vs. HG MIBC: p  = .82; Student's t ‐test). Overall, the DNAm profile distinguishes MIBC from NMIBC and normal urine. Targeted‐sequencing‐based DNAm signature classifiers accurately classify LG NMIBC tissues from HG MIBC and could detect tumours in urine at a limit of detection of less than .5%. In tumour tissues, DNAm accurately classifies pathology, thus outperforming genomic mutation or RNA expression profiles. In the independent validation cohort, pre‐surgery urine ctDNA methylation outperforms fluorescence in situ hybridization (FISH) assay to detect HG BLCA ( n  = 54) with 100% sensitivity (95% CI: 82.5%–100%) and LG BLCA ( n  = 26) with 62% sensitivity (95% CI: 51.3%–72.7%), both at 100% specificity (non‐BLCA: n  = 72; 95% CI: 84.1%–100%). Pre‐surgery urine ctDNA methylation signature correlates with pathology and predicts recurrence and metastasis. Post‐surgery urine ctDNA methylation ( n  = 61) accurately predicts recurrence‐free survival within 180 days, with 100% accuracy. Conclusion With the discovery of BLCA‐specific DNAm signatures, targeted sequencing of ctDNA methylation outperforms FISH and DNA mutation to detect tumours, predict recurrence and make prognoses.
    Type of Medium: Online Resource
    ISSN: 2001-1326 , 2001-1326
    URL: Issue
    URL: Article
    DOI: 10.1002/ctm2.v12.8
    DOI: 10.1002/ctm2.1008
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2697013-2
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