45,453 results match your criteria human oncogenic

Comprehensive analysis of clinical prognosis and molecular immune characterization of tropomyosin 4 in pancreatic cancer.

Invest New Drugs 2021 May 13. Epub 2021 May 13.

Tianjin Third Central Hospital, 83 Jintang Road, Hedong District, Tianjin, 300170, China.

Pancreatic cancer (PC) is one of the most lethal human solid malignancies with devastating prognosis, making biomarker detection considerably important. Immune infiltrates in microenvironment is associated with patients' survival in PC. The role of Tropomyosin 4 (TPM4) gene in PC has not been reported. Read More

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Single-PanIN-seq unveils that deficiency promotes pancreatic tumorigenesis by attenuating -induced senescence.

Elife 2021 May 13;10. Epub 2021 May 13.

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States.

is one of the most frequently mutated epigenetic regulators in a wide spectrum of cancers. Recent studies have shown that deficiency induces global changes in the epigenetic landscape of enhancers and promoters. These broad and complex effects make it challenging to identify the driving mechanisms of deficiency in promoting cancer progression. Read More

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The extracellular-regulated protein kinase 5 (ERK5) enhances metastatic burden in triple-negative breast cancer through focal adhesion protein kinase (FAK)-mediated regulation of cell adhesion.

Oncogene 2021 May 12. Epub 2021 May 12.

Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.

There is overwhelming clinical evidence that the extracellular-regulated protein kinase 5 (ERK5) is significantly dysregulated in human breast cancer. However, there is no definite understanding of the requirement of ERK5 in tumor growth and metastasis due to very limited characterization of the pathway in disease models. In this study, we report that a high level of ERK5 is a predictive marker of metastatic breast cancer. Read More

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Environmental DNA monitoring of oncogenic viral shedding and genomic profiling of sea turtle fibropapillomatosis reveals unusual viral dynamics.

Commun Biol 2021 May 12;4(1):565. Epub 2021 May 12.

The Whitney Laboratory for Marine Bioscience and Sea Turtle Hospital, University of Florida, St. Augustine, FL, USA.

Pathogen-induced cancers account for 15% of human tumors and are a growing concern for endangered wildlife. Fibropapillomatosis is an expanding virally and environmentally co-induced sea turtle tumor epizootic. Chelonid herpesvirus 5 (ChHV5) is implicated as a causative virus, but its transmission method and specific role in oncogenesis and progression is unclear. Read More

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Cancer-associated mutations reveal a novel role for EpCAM as an inhibitor of cathepsin-L and tumor cell invasion.

BMC Cancer 2021 May 12;21(1):541. Epub 2021 May 12.

Department of Surgery, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8109, Saint Louis, MO, 63110, USA.

Background: EpCAM (Epithelial cell adhesion molecule) is often dysregulated in epithelial cancers. Prior studies implicate EpCAM in the regulation of oncogenic signaling pathways and epithelial-to-mesenchymal transition. It was recently demonstrated that EpCAM contains a thyroglobulin type-1 (TY-1) domain. Read More

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Targeting SUMOylation dependency in human cancer stem cells through a unique SAE2 motif revealed by chemical genomics.

Cell Chem Biol 2021 May 7. Epub 2021 May 7.

Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON L8S 4K1, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8S 4K1, Canada. Electronic address:

Natural products (NPs) encompass a rich source of bioactive chemical entities. Here, we used human cancer stem cells (CSCs) in a chemical genomics campaign with NP chemical space to interrogate extracts from diverse strains of actinomycete for anti-cancer properties. We identified a compound (McM25044) capable of selectively inhibiting human CSC function versus normal stem cell counterparts. Read More

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Dissecting Oncogenic RAS Signaling in Melanoma Development in Genetically Engineered Zebrafish Models.

Methods Mol Biol 2021 ;2262:411-422

Faculty of Biology, Medicine and Health, School of Biological Sciences, The University of Manchester, Manchester, UK.

Hyper-activation of RAS signaling pathways causes cancer, including melanoma, and RAS signaling pathways have been successfully targeted using drugs for patient benefit. The available drugs alone cannot cure cancer, however, and so investigation continues into RAS signaling pathways, with the goal of identifying further actionable targets. The zebrafish can be used to model human malignancies, and genetic modification of zebrafish to incorporate selective disease-associated genetic alterations is practicable. Read More

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January 2021

Probing RAS Function with Monobodies.

Methods Mol Biol 2021 ;2262:281-302

Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA.

RAS is frequently mutated in human cancers with nearly 20% of all cancers harboring mutations in one of three RAS isoforms (KRAS, HRAS, or NRAS). Furthermore, RAS proteins are critical oncogenic drivers of tumorigenesis. As such, RAS has been a prime focus for development of targeted cancer therapeutics. Read More

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January 2021

Regulation of the Small GTPase Ras and Its Relevance to Human Disease.

Methods Mol Biol 2021 ;2262:19-43

Institute of Molecular Cell Biology, Center for Molecular Biomedicine, University Hospital Jena, Jena, Germany.

Ras research has experienced a considerable boost in recent years, not least prompted by the Ras initiative launched by the NCI in 2013 ( https://www.cancer.gov/research/key-initiatives/ras ), accompanied and conditioned by a strongly reinvigorated determination within the Ras community to develop therapeutics attacking directly the Ras oncoproteins. Read More

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January 2021

DeepVISP: Deep Learning for Virus Site Integration Prediction and Motif Discovery.

Adv Sci (Weinh) 2021 05 8;8(9):2004958. Epub 2021 Mar 8.

Center for Precision Health School of Biomedical Informatics The University of Texas Health Science Center at Houston (UTHealth) Houston TX 77030 USA.

Approximately 15% of human cancers are estimated to be attributed to viruses. Virus sequences can be integrated into the host genome, leading to genomic instability and carcinogenesis. Here, a new deep convolutional neural network (CNN) model is developed with attention architecture, namely DeepVISP, for accurately predicting oncogenic virus integration sites (VISs) in the human genome. Read More

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MiRNA-202-5p promotes Colorectal Carcinogenesis through suppression of PTEN.

J Cancer 2021 31;12(11):3154-3163. Epub 2021 Mar 31.

Department of Immunology, the school of Basic Medical Sciences, Anhui Medical University, Hefei, China, 230032.

Colorectal cancer (CRC) is still one of the leading causes of cancer-associated death in the modern society. The biological function of miR-202-5p for CRC development remains controversial, largely due to the fact that miR-202-5p can be tumor-suppressive or oncogenic in different contexts. Obtained results indicated that aberrant expression of miR-202-5p was observed in majority of human CRC samples and miR-202-5p was transcriptionally up-regulated by c-Myc. Read More

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Selective and noncovalent targeting of RAS mutants for inhibition and degradation.

Nat Commun 2021 May 11;12(1):2656. Epub 2021 May 11.

Perlmutter Cancer Center, New York University Langone Health, New York, NY, USA.

Activating mutants of RAS are commonly found in human cancers, but to date selective targeting of RAS in the clinic has been limited to KRAS(G12C) through covalent inhibitors. Here, we report a monobody, termed 12VC1, that recognizes the active state of both KRAS(G12V) and KRAS(G12C) up to 400-times more tightly than wild-type KRAS. The crystal structures reveal that 12VC1 recognizes the mutations through a shallow pocket, and 12VC1 competes against RAS-effector interaction. Read More

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Phase separation of EML4-ALK in firing downstream signaling and promoting lung tumorigenesis.

Cell Discov 2021 May 11;7(1):33. Epub 2021 May 11.

State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, China.

EML4-ALK fusion, observed in about 3%-7% of human lung adenocarcinoma, is one of the most important oncogenic drivers in initiating lung tumorigenesis. However, it still remains largely unknown about how EML4-ALK fusion exactly fires downstream signaling and drives lung cancer formation. We here find that EML4-ALK variant 1 (exon 1-13 of EML4 fused to exon 20-29 of ALK) forms condensates via phase separation in the cytoplasm of various human cancer cell lines. Read More

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The stem cell-specific protein TRIM71 inhibits maturation and activity of the pro-differentiation miRNA let-7 via two independent molecular mechanisms.

RNA 2021 May 11. Epub 2021 May 11.

Life and Medical Sciences Institute (LIMES), University of Bonn.

The stem cell-specific RNA-binding protein TRIM71/LIN-41 was the first identified target of the pro-differentiation and tumor suppressor miRNA let-7. TRIM71 has essential functions in embryonic development and a proposed oncogenic role in several cancer types, such as hepatocellular carcinoma. Here, we show that TRIM71 regulates let-7 expression and activity via two independent mechanisms. Read More

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Reprogramming of the esophageal squamous carcinoma epigenome by SOX2 promotes ADAR1 dependence.

Nat Genet 2021 May 10. Epub 2021 May 10.

Herbert Irving Comprehensive Cancer Center, Division of Digestive and Liver Diseases, Department of Medicine, Columbia University, New York, NY, USA.

Esophageal squamous cell carcinomas (ESCCs) harbor recurrent chromosome 3q amplifications that target the transcription factor SOX2. Beyond its role as an oncogene in ESCC, SOX2 acts in development of the squamous esophagus and maintenance of adult esophageal precursor cells. To compare Sox2 activity in normal and malignant tissue, we developed engineered murine esophageal organoids spanning normal esophagus to Sox2-induced squamous cell carcinoma and mapped Sox2 binding and the epigenetic and transcriptional landscape with evolution from normal to cancer. Read More

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Arginine methyltransferase PRMT5 methylates and stabilizes KLF5 via decreasing its phosphorylation and ubiquitination to promote basal-like breast cancer.

Cell Death Differ 2021 May 10. Epub 2021 May 10.

Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China.

Krüppel-like factor 5 (KLF5) is an oncogenic factor that is highly expressed in basal-like breast cancer (BLBC) and promotes cell proliferation, survival, migration, stemness, and tumor growth; however, its posttranslational modifications are poorly defined. Protein arginine methyltransferase 5 (PRMT5) is also an oncogene implicated in various carcinomas, including breast cancer. In this study, we found that PRMT5 interacts with KLF5 and catalyzes the di-methylation of KLF5 at Arginine 57 (R57) in a methyltransferase activity-dependent manner in BLBC cells. Read More

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Cyclooxygenase-2 induces neoplastic transformation by inhibiting p53-dependent oncogene-induced senescence.

Sci Rep 2021 May 10;11(1):9853. Epub 2021 May 10.

Department of Biochemistry and Molecular Biology, Kangwon National University School of Medicine, Chuncheon, 24341, South Korea.

Much in vivo evidence indicates that cyclooxygenase-2 (COX-2) is deeply involved in tumorigenesis. Although it has been proposed that COX-2-derived pro-inflammatory prostanoids mediate the tumorigenic activity of COX-2, the tumorigenic mechanisms of COX-2 are not yet fully understood. Here, we investigated the mechanism by which COX-2 causes transformation from normal cells to malignant cells by using normal murine or human cells. Read More

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Cryo-EM structure of SETD2/Set2 methyltransferase bound to a nucleosome containing oncohistone mutations.

Cell Discov 2021 May 11;7(1):32. Epub 2021 May 11.

Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200125, China.

Substitution of lysine 36 with methionine in histone H3.3 (H3.3K36M) is an oncogenic mutation that inhibits SETD2-mediated histone H3K36 tri-methylation in tumors. Read More

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Genetic instability and anti-HPV immune response as drivers of infertility associated with HPV infection.

Infect Agent Cancer 2021 May 10;16(1):29. Epub 2021 May 10.

Istituto Nazionale Tumori - IRCCS "Fondazione Pascale", Naples, Italy.

Human papillomavirus (HPV) is a sexually transmitted infection common among men and women of reproductive age worldwide. HPV viruses are associated with epithelial lesions and cancers. HPV infections have been shown to be significantly associated with many adverse effects in reproductive function. Read More

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TET1 upregulation drives cancer cell growth through aberrant enhancer hydroxymethylation of HMGA2 in hepatocellular carcinoma.

Cancer Sci 2021 May 10. Epub 2021 May 10.

Genome Science Division, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan.

Ten-eleven translocation 1 (TET1) is an essential methylcytosine dioxygenase of the DNA demethylation pathway. Despite its dysregulation being known to occur in human cancer, the role of TET1 remains poorly understood. In this study, we report that TET1 promotes cell growth in human liver cancer. Read More

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Oncohistones: A Roadmap to Stalled Development.

FEBS J 2021 May 10. Epub 2021 May 10.

Division of Experimental Medicine, McGill University, Montreal, Quebec, Canada.

Since the discovery of recurrent mutations in histone H3 variants in pediatric brain tumours, so-called 'oncohistones' have been identified in various cancers. While their mechanism of action remains under active investigation, several studies have shed light on how they promote genome-wide epigenetic perturbations. These findings converge on altered post-translational modifications on two key lysine (K) residues of the H3 tail, K27 and K36, which regulate several cellular processes, including those linked to cell differentiation during development. Read More

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The Human Bone Marrow Is Host to the DNAs of Several Viruses.

Front Cell Infect Microbiol 2021 22;11:657245. Epub 2021 Apr 22.

Department of Virology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

The long-term impact of viruses residing in the human bone marrow (BM) remains unexplored. However, chronic inflammatory processes driven by single or multiple viruses could significantly alter hematopoiesis and immune function. We performed a systematic analysis of the DNAs of 38 viruses in the BM. Read More

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A Pancancer Analysis of the Expression Landscape and Clinical Relevance of Fibroblast Growth Factor Receptor 2 in Human Cancers.

Front Oncol 2021 21;11:644854. Epub 2021 Apr 21.

Department of Pathology, Xiangya Hospital, Central South University, Changsha, China.

Fibroblast growth factor receptor 2 (FGFR2) is frequently altered in tumors and one of the top therapeutic targets in cholangiocarcinoma (CHOL) with fusions. Although there have been several studies on individual tumors, a comprehensive analysis of genetic aberrations and their simultaneous clinical implications across different tumors have not been reported. In this study, we used the large comprehensive datasets available, covering over 10,000 tumor samples across more than 30 cancer types, to analyze abnormal expression, methylation, alteration (mutations/fusions and amplification/deletion), and their clinical associations. Read More

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Oncogenic WIP1 phosphatase attenuates the DNA damage response and sensitizes p53 mutant Jurkat cells to apoptosis.

Oncol Lett 2021 Jun 19;21(6):479. Epub 2021 Apr 19.

Department of Medical Biology, Institute of Health Sciences, University of Aydin Adnan Menderes, 09010 Aydin, Turkey.

Wild-type (wt) p53-induced phosphatase 1 (Wip1), encoded by the protein phosphatase, Mg/Mn dependent 1D (PPM1D) gene, is a serine/threonine phosphatase induced upon genotoxic stress in a p53-dependent manner. Wip1/PPM1D is frequently overexpressed, amplified and mutated in human solid tumors harboring wt p53 and is thus currently recognized as an oncogene. Oncogenic Wip1 dampens cellular stress responses, such as cell cycle checkpoints, apoptosis and senescence, and consequently increases resistance to anticancer therapeutics. Read More

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Dysregulation of the ESRP2-NF2-YAP/TAZ axis promotes hepatobiliary carcinogenesis in non-alcoholic fatty liver disease.

J Hepatol 2021 May 5. Epub 2021 May 5.

Department of Medicine, Duke University, Duke University Health System, Durham, NC, USA. Electronic address:

Background & Aims: Nonalcoholic Fatty Liver Disease (NAFLD), the hepatic correlate of the metabolic syndrome, is a major risk factor for hepatobiliary cancer (HBC). Although chronic inflammation is thought to be the root cause of all these diseases, the mechanism whereby it promotes HBC in NAFLD remains poorly understood. Here we aim to evaluate the hypothesis that inflammation-related dysregulation of the ESRP2-NF2-YAP/TAZ axis promotes HB carcinogenesis. Read More

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Specific inhibition of oncogenic RAS using cell-permeable RAS-binding domains.

Cell Chem Biol 2021 May 4. Epub 2021 May 4.

United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu 501-1193, Japan. Electronic address:

Oncogenic RAS proteins, common oncogenic drivers in many human cancers, have been refractory to conventional small-molecule and macromolecule inhibitors due to their intracellular localization and the lack of druggable pockets. Here, we present a feasible strategy for designing RAS inhibitors that involves intracellular delivery of RAS-binding domain (RBD), a nanomolar-affinity specific ligand of RAS. Screening of 51 different combinations of RBD and cell-permeable peptides has identified Pen-cRaf-v1 as a cell-permeable pan-RAS inhibitor capable of targeting both G12C and non-G12C RAS mutants. Read More

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LncRNA SAMD12-AS1 promotes the progression of gastric cancer via DNMT1/p53 axis.

Arch Med Res 2021 May 4. Epub 2021 May 4.

Department of General Surgery, The No.967 Hospital of PLA Joint Logistics Support Force, Postgraduate Culture Base of Jinzhou Medical University, Dalian, China; Department of General Surgery, The No.967 Hospital of PLA Joint Logistics Support Force, Postgraduate Culture Base of Dalian Medical University, Dalian, China. Electronic address:

Background: Long noncoding RNAs (lncRNAs) are essential modulators of cancers initiation and progression via regulating gene expression and biological behaviors. LncRNA SAMD12-AS1 has been validated to promote the progression of several cancers, while its role in gastric cancer (GC) remains unclear. This study aims to explore the role of LncRNA SAMD12-AS1 in GC. Read More

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Genotype-specific prevalence of human papillomavirus infection in asymptomatic Peruvian women: a community-based study.

BMC Res Notes 2021 May 7;14(1):172. Epub 2021 May 7.

Barcelona Research Center for Multiscale Science and Engineering, Departament D'Enginyeria Química, EEBE, Universitat Politècnica de Catalunya (UPC), Barcelona, Spain.

Objective: To determine the general and genotype-specific prevalence of HPV and to identify potential risk factors for the infection in a population-based screening of Peruvian women.

Results: A total of 524 samples were analyzed by PCR and a total of 100 HPV positive samples were found, of which 89 were high-risk, 19 were probably oncogenic, 9 were low-risk and 27 other HPV types. The 26-35 and 36-45 age groups showed the highest proportion of HPV positive samples with a total of 37% (37/100) and 30% (30/100), respectively. Read More

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Family with sequence similarity 83 member A promotes tumor cell proliferation and metastasis and predicts poor prognosis in cervical cancer.

Pathol Res Pract 2021 Apr 15;222:153450. Epub 2021 Apr 15.

Department of Obstetrics and Gynecology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, Guangdong, China. Electronic address:

Family with sequence similarity 83 member A (FAM83A) is a member of the FAM83 family and is proven to have oncogenic properties in several cancers. However, the mechanisms of FAM83A in human cervical cancer (CC) progression are unknown. Here, we found that FAM83A is highly expressed in CC tissues and cell lines through western blot and qRT-PCR. Read More

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ADORA1 promotes nasopharyngeal carcinoma cell progression through regulation of PI3K/AKT/GSK-3β/β-catenin signaling.

Life Sci 2021 May 4;278:119581. Epub 2021 May 4.

Department of Radiation Oncology, Yue Bei People's Hospital, Shaoguan, Guangdong, China.

Aims: For most human cancers, the expression pattern and biological function of ADORA1 (Adenosine A1 Receptor) are largely unknown. This study has been designed to explore the clinical significance and the mechanism of ADORA1 in nasopharyngeal carcinoma (NPC) cells.

Materials And Methods: The level of ADORA1 in NPC and its adjacent tissues was analyzed by IHC, real-time PCR and western blotting. Read More

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