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Molecular Oncology Jul 2024K. Liu, J.-D. Ni, W.-Z. Li, B.-Q. Pan, Y.-T. Yang, Q. Xia and J. Huang, "The Sp1/FOXC1/HOTTIP/LATS2/YAP/β-Catenin Cascade Promotes Malignant and Metastatic Progression...
K. Liu, J.-D. Ni, W.-Z. Li, B.-Q. Pan, Y.-T. Yang, Q. Xia and J. Huang, "The Sp1/FOXC1/HOTTIP/LATS2/YAP/β-Catenin Cascade Promotes Malignant and Metastatic Progression of Osteosarcoma," Molecular Oncology 14, no. 10 (2020): 2678-2695, https://doi.org/10.1002/1878-0261.12760. The above article, version of record published online on 29 August 2020 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor in Chief, Kevin Ryan and John Wiley and Sons Ltd. The decision to retract the manuscript has been made due to insufficient explanation or provision of appropriate raw data to justify the duplicated ruler, which have appeared in other publications, along with overlap between different panels of Figs. 2E, 3F, and 4F. The editors consider the conclusions substantially compromised and are therefore retracting the paper.
PubMed: 38949165
DOI: 10.1002/1878-0261.13692 -
Colorectal Disease : the Official... Jul 2024Follow-up for colorectal cancer (CRC) necessitates regular monitoring of carcinoembryonic antigen (CEA) at the hospital. Capillary home-based blood collection, including...
Feasibility, reliability and satisfaction of (automated) capillary carcinoembryonic antigen measurements for future home-based blood sampling: the prospective CASA-I study.
AIM
Follow-up for colorectal cancer (CRC) necessitates regular monitoring of carcinoembryonic antigen (CEA) at the hospital. Capillary home-based blood collection, including minimally invasive techniques such as lancet sampling or an automated upper arm device (TAP-II), has the potential to replace a significant portion of hospital-based blood sampling, thereby enhancing self-reliance and quality of life. The objectives of this study were to assess the feasibility, reliability and preference for CEA blood collection.
METHODS
Baseline venous and capillary (by lancet and TAP-II) blood samples were collected from 102 participants, including 20 CRC patients with elevated CEA levels, 60 CRC patients undergoing postoperative outpatient monitoring and 20 healthy volunteers. The second group performed capillary blood collections at home on two consecutive follow-up appointments and subsequently sent them to the hospital. Satisfaction was assessed via patient reported outcome measures on pain, burden, ease of use and preference.
RESULTS
The Pearson's correlation test of all usable samples resulted in a linear coefficient of 0.998 (95% CI 0.997-0.998) for the TAP-II method and 0.997 (95% CI 0.996-0.998) for the lancet method, both compared to venipuncture. Following the initial blood collection, 86% of the participants (n = 102) favoured the TAP-II, rating it as the least painful and burdensome option. After two home-based blood samples, the preference for the TAP-II method persisted, with 64% of the patients endorsing its use.
CONCLUSION
This study demonstrated the feasibility of home-based capillary sampling of CEA. The TAP-II blood collection is the most reliable method and is preferred by patients over venipuncture and lancet sampling.
PubMed: 38949106
DOI: 10.1111/codi.17085 -
The Journal of Gene Medicine Jul 2024Colorectal cancer is the third most common malignancy worldwide and is one of the leading causes of cancer-related mortality. Ubiquitin-specific peptidase 18 (USP18)...
BACKGROUND
Colorectal cancer is the third most common malignancy worldwide and is one of the leading causes of cancer-related mortality. Ubiquitin-specific peptidase 18 (USP18) protein has been reported to exert different tumor-related effects in distinct tumor types. Here, we initially investigated the expression and signaling pathways of USP18 in colon adenocarcinoma (COAD).
METHODS
A quantitative real-time PCR was conducted to evaluate the mRNA level of USP18 in cultured cells. Immunohistochemical staining was used to explore the protein expression of USP18 in clinical COAD samples. Specific knockdown was achieved by transient transfection of small interfering RNAs into SW480 and HT29 cells using Lipo3000. Cell conting kit-8 assay, transwell assay and matrigel-transwell assays were conducted to evaluate proliferation, migration and invasion capacities, respectively. Western blotting was performed to analyze downstream signaling pathways. A chi-squared test and univariate and multivariate analyses were used to evaluate the clinical data. Xenografts from mice model were assessed to validate the in vitro findings.
RESULTS
Higher USP18 level was identified in COAD tissues and was positively correlated with advanced tumor stage. High USP18 protein expression indicated poorer prognosis of COAD patients. Silencing USP18 suppressed COAD cell proliferation and invasion via destabilizing extracellular signal-regulated kinase (ERK) protein and suppressing ERK downstream pathways. Simultaneously silencing interferon-stimulated gene 15 (ISG15) with USP18 can partially rescue the tumor cell viability, indicating its involvement in USP18 signaling. The oncogenic effects of USP18 were also confirmed in mice models.
CONCLUSIONS
USP18 plays oncogenic effects in colon adenocarcinoma via ISG15-ERK pathways. High USP18 expression indicates poor clinical outcomes for colon adenocarcinoma patients.
Topics: Humans; Ubiquitin Thiolesterase; Animals; Cell Proliferation; Mice; Adenocarcinoma; Colonic Neoplasms; Male; Cell Movement; Female; Gene Expression Regulation, Neoplastic; Signal Transduction; Cell Line, Tumor; Disease Progression; Middle Aged; Prognosis; MAP Kinase Signaling System; Extracellular Signal-Regulated MAP Kinases; HT29 Cells; Mice, Nude
PubMed: 38949077
DOI: 10.1002/jgm.3709 -
The Journal of Gene Medicine Jul 2024The present study aimed to identify dysregulated genes, molecular pathways, and regulatory mechanisms in human papillomavirus (HPV)-associated cervical cancers. We have...
BACKGROUND
The present study aimed to identify dysregulated genes, molecular pathways, and regulatory mechanisms in human papillomavirus (HPV)-associated cervical cancers. We have investigated the disease-associated genes along with the Gene Ontology, survival prognosis, transcription factors and the microRNA (miRNA) that are involved in cervical carcinogenesis, enabling a deeper comprehension of cervical cancer linked to HPV.
METHODS
We used 10 publicly accessible Gene Expression Omnibus (GEO) datasets to examine the patterns of gene expression in cervical cancer. Differentially expressed genes (DEGs), which showed a clear distinction between cervical cancer and healthy tissue samples, were analyzed using the GEO2R tool. Additional bioinformatic techniques were used to carry out pathway analysis and functional enrichment, as well as to analyze the connection between altered gene expression and HPV infection.
RESULTS
In total, 48 DEGs were identified to be differentially expressed in cervical cancer tissues in comparison to healthy tissues. Among DEGs, CCND1, CCNA2 and SPP1 were the key dysregulated genes involved in HPV-associated cervical cancer. The five common miRNAs that were identified against these genes are miR-7-5p, miR-16-5p, miR-124-3p, miR-10b-5p and miR-27a-3p. The hub-DEGs targeted by miRNA hsa-miR-27a-3p are controlled by the common transcription factor SP1.
CONCLUSIONS
The present study has identified DEGs involved in HPV-associated cervical cancer progression and the various molecular pathways and transcription factors regulating them. These findings have led to a better understanding of cervical cancer resulting in the development and identification of possible therapeutic and intervention targets, respectively.
Topics: Uterine Cervical Neoplasms; Humans; MicroRNAs; Female; Gene Expression Regulation, Neoplastic; Computational Biology; Gene Expression Profiling; Gene Regulatory Networks; Papillomavirus Infections; Gene Ontology; Biomarkers, Tumor; Prognosis; Databases, Genetic; Signal Transduction
PubMed: 38949075
DOI: 10.1002/jgm.3713 -
The Journal of Gene Medicine Jul 2024Aggrephagy, a type of autophagy, degrades the aggregation of misfolded protein in cells. However, the role of aggrephagy in multiple myeloma (MM) has not been fully...
Aggrephagy, a type of autophagy, degrades the aggregation of misfolded protein in cells. However, the role of aggrephagy in multiple myeloma (MM) has not been fully demonstrated. In this study, we first investigated the correlation between aggrephagy signaling, MM immune microenvironment composition and disease prognosis. Single-cell RNA-seq data, including the expression profiles of 12,187 single cells from seven MM bone marrow (BM) and seven healthy BM samples, were analyzed by non-negative matrix factorization for 44 aggrephagy-related genes. Bulk RNA-seq cohorts from the Gene Expression Omnibus database were used to evaluate the prognostic value of aggrephagy-related immune cell subtypes and predict immune checkpoint blockade immunotherapeutic response in MM. Compared with healthy BM, MM BM exhibited different patterns of aggrephagy-related gene expression. In MM BM, macrophages, CD8 T cells, B cells and natural killer cells could be grouped into four to nine aggrephagy-related subclusters. The signature of aggrephagy signaling molecule expression in the immune cells correlates with the patient's prognosis. Our investigation provides a novel view of aggrephagy signaling in MM tumor microenvironment cells, which might be a prognostic indicator and potential target for MM treatment.
Topics: Multiple Myeloma; Humans; Tumor Microenvironment; Single-Cell Analysis; Prognosis; Signal Transduction; Gene Expression Regulation, Neoplastic; Autophagy; Gene Expression Profiling; Biomarkers, Tumor; Transcriptome
PubMed: 38949072
DOI: 10.1002/jgm.3712 -
Singapore Medical Journal Jun 2024
PubMed: 38949060
DOI: 10.4103/singaporemedj.SMJ-2023-134 -
The Journal of Clinical Investigation Jul 2024
Topics: Humans; Killer Cells, Natural; Animals; Glucuronidase; Immunologic Surveillance; Neoplasm Invasiveness; Mice; Neoplasms
PubMed: 38949030
DOI: 10.1172/JCI183295 -
The Journal of Clinical Investigation Jul 2024Ubiquitination plays an essential role in protein stability, subcellular localization, and interactions. Crosstalk between different types of ubiquitination results in...
Ubiquitination plays an essential role in protein stability, subcellular localization, and interactions. Crosstalk between different types of ubiquitination results in distinct biological outcomes for proteins. However, the role of ubiquitination-related crosstalk in lymph node (LN) metastasis and the key regulatory factors controlling this process have not been determined. Using high-throughput sequencing, we found that ubiquitin-conjugating enzyme E2 C (UBE2C) was overexpressed in bladder cancer (BCa) and was strongly associated with an unfavorable prognosis. Overexpression of UBE2C increased BCa lymphangiogenesis and promoted LN metastasis both in vitro and in vivo. Mechanistically, UBE2C mediated sodium-coupled neutral amino acid transporter 2 (SNAT2) monoubiquitination at lysine 59 to inhibit K63-linked polyubiquitination at lysine 33 of SNAT2. Crosstalk between monoubiquitination and K63-linked polyubiquitination increased SNAT2 membrane protein levels by suppressing epsin 1-mediated (EPN1-mediated) endocytosis. SNAT2 facilitated glutamine uptake and metabolism to promote VEGFC secretion, ultimately leading to lymphangiogenesis and LN metastasis in patients with BCa. Importantly, inhibition of UBE2C significantly attenuated BCa lymphangiogenesis in a patient-derived xenograft model. Our results reveal the mechanism by which UBE2C mediates crosstalk between the monoubiquitination and K63-linked polyubiquitination of SNAT2 to promote BCa metastasis and identify UBE2C as a promising target for treating LN-metastatic BCa.
Topics: Ubiquitin-Conjugating Enzymes; Humans; Ubiquitination; Urinary Bladder Neoplasms; Animals; Lymphatic Metastasis; Mice; Cell Line, Tumor; Lymphangiogenesis; Female; Male; Vascular Endothelial Growth Factor C; Neoplasm Proteins; Minor Histocompatibility Antigens; Amino Acid Transport System ASC
PubMed: 38949026
DOI: 10.1172/JCI179122 -
The Journal of Clinical Investigation Jul 2024Cancer risk is modulated by hereditary and somatic mutations, exposures, age, sex, and gender. The mechanisms by which sex and gender work alone and in combination with... (Review)
Review
Cancer risk is modulated by hereditary and somatic mutations, exposures, age, sex, and gender. The mechanisms by which sex and gender work alone and in combination with other cancer risk factors remain underexplored. In general, cancers that occur in both the male and female sexes occur more commonly in XY compared with XX individuals, regardless of genetic ancestry, geographic location, and age. Moreover, XY individuals are less frequently cured of their cancers, highlighting the need for a greater understanding of sex and gender effects in oncology. This will be necessary for optimal laboratory and clinical cancer investigations. To that end, we review the epigenetics of sexual differentiation and its effect on cancer hallmark pathways throughout life. Specifically, we will touch on how sex differences in metabolism, immunity, pluripotency, and tumor suppressor functions are patterned through the epigenetic effects of imprinting, sex chromosome complement, X inactivation, genes escaping X inactivation, sex hormones, and life history.
Topics: Humans; Female; Neoplasms; Male; Epigenesis, Genetic; Sex Characteristics; Animals; X Chromosome Inactivation; Gonadal Steroid Hormones; Genomic Imprinting
PubMed: 38949020
DOI: 10.1172/JCI180071 -
JPMA. the Journal of the Pakistan... Jun 2024
Topics: Humans; Myasthenia Gravis; Adrenal Cortex Hormones; Glucocorticoids
PubMed: 38949011
DOI: 10.47391/JPMA.10214