809 results match your criteria oncogenic promoters


Integrated transcription factor profiling with transcriptome analysis identifies L1PA2 transposons as global regulatory modulators in a breast cancer model.

Sci Rep 2021 Apr 13;11(1):8083. Epub 2021 Apr 13.

School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD, 4072, Australia.

While transposons are generally silenced in somatic tissues, many transposons escape epigenetic repression in epithelial cancers, become transcriptionally active and contribute to the regulation of human gene expression. We have developed a bioinformatic pipeline for the integrated analysis of transcription factor binding and transcriptomic data to identify transposon-derived promoters that are activated in specific diseases and developmental states. We applied this pipeline to a breast cancer model, and found that the L1PA2 transposon subfamily contributes abundant regulatory sequences to co-ordinated transcriptional regulation in breast cancer. Read More

View Article and Full-Text PDF

Homeodomain only protein X (HOPX) has an oncogenic activity during squamous skin carcinogenesis.

J Invest Dermatol 2021 Apr 9. Epub 2021 Apr 9.

Department of Dermatology and Venereology, University Hospital Centre (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland. Electronic address:

Cutaneous squamous cell carcinomas (cSCC) are frequent heterogeneous tumours, arising from sun-exposed regions of the skin and characterized by complex pathogenesis. HOPX is a member of the homeodomain-containing superfamily of proteins, holding an atypical homeodomain unable to bind DNA. First discovered in the heart as a regulator of cardiac development, in skin HOPX modulates terminal differentiation of keratinocytes. Read More

View Article and Full-Text PDF

Transcriptional dysregulation by aberrant enhancer activation and rewiring in cancer.

Cancer Sci 2021 Mar 17. Epub 2021 Mar 17.

Department of Molecular Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan.

Cell identity is controlled by regulatory elements, such as promoters, enhancers, and insulators, within the genome. These regulatory elements interact in the nucleus and form tissue-specific chromatin structures. Dysregulation of these elements and their interactions can lead to loss of cell identity and promote the development of diseases such as cancer. Read More

View Article and Full-Text PDF

Characterization of Gene Isoforms and Targets Across Cell Types Reveals Highly Conserved Networks.

Front Genet 2021 22;12:613808. Epub 2021 Feb 22.

Laboratorio de Transducción de Señales y Cáncer, Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Biológicas, Universidad de Concepción, Concepción, Chile.

The SALL2 transcription factor, an evolutionarily conserved gene through vertebrates, is involved in normal development and neuronal differentiation. In disease, SALL2 is associated with eye, kidney, and brain disorders, but mainly is related to cancer. Some studies support a tumor suppressor role and others an oncogenic role for SALL2, which seems to depend on the cancer type. Read More

View Article and Full-Text PDF
February 2021

LY6K-AS lncRNA is a lung adenocarcinoma prognostic biomarker and regulator of mitotic progression.

Oncogene 2021 Apr 5;40(13):2463-2478. Epub 2021 Mar 5.

Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.

Recent advances in genomics unraveled several actionable mutational drivers in lung cancer, leading to promising therapies such as tyrosine kinase inhibitors and immune checkpoint inhibitors. However, the tumors' acquired resistance to the newly-developed as well as existing therapies restricts life quality improvements. Therefore, we investigated the noncoding portion of the human transcriptome in search of alternative actionable targets. Read More

View Article and Full-Text PDF

G-quadruplexes: a promising target for cancer therapy.

Mol Cancer 2021 02 25;20(1):40. Epub 2021 Feb 25.

Department of Oncology, Hematology, Rheumatology and Immune-Oncology, University Hospital Bonn, 53127, Bonn, Germany.

DNA and RNA can fold into a variety of alternative conformations. In recent years, a particular nucleic acid structure was discussed to play a role in malignant transformation and cancer development. This structure is called a G-quadruplex (G4). Read More

View Article and Full-Text PDF
February 2021

Circ_0006948 Contributes to Cell Growth, Migration, Invasion and Epithelial-Mesenchymal Transition in Esophageal Carcinoma.

Dig Dis Sci 2021 Feb 25. Epub 2021 Feb 25.

Department of Gastroenterology, Jinan Central Hospital Affiliated to Shandong First Medical University, No.105 Jiefang Road, Lixia District, Jinan, 250013, Shandong Province, China.

Background: Circular RNAs (circRNAs) can act as promoters or inhibitors in cancer progression. Has_circ_0006948 (circ_0006948) was reported to aggravate the malignant behaviors of esophageal carcinoma (EC).

Aims: This study focused on investigating the molecular mechanism of circ_0006948 in EC progression. Read More

View Article and Full-Text PDF
February 2021

Porcine model elucidates function of p53 isoform in carcinogenesis and reveals novel circTP53 RNA.

Oncogene 2021 Mar 18;40(10):1896-1908. Epub 2021 Feb 18.

Chair of Livestock Biotechnology, Technische Universität München, Munich, Germany.

Recent years have seen an increasing number of genetically engineered pig models of human diseases including cancer. We previously generated pigs with a modified TP53 allele that carries a Cre-removable transcriptional stop signal in intron 1, and an oncogenic mutation TP53 (orthologous to human TP53) in exon 5. Pigs with the unrecombined mutant allele (flTP53) develop mainly osteosarcoma but also nephroblastomas and lymphomas. Read More

View Article and Full-Text PDF

Gallic acid inhibits Kaposi's Sarcoma-associated herpesvirus lytic reactivation by suppressing RTA transcriptional activities.

Food Sci Nutr 2021 Feb 3;9(2):847-854. Epub 2020 Dec 3.

Central Laboratory The Fourth Affiliated Hospital Zhejiang University School of Medicine N1 Shangcheng Avenue Yiwu 322000 China.

Kaposi's sarcoma-associated herpesvirus (KSHV), an oncogenic virus, has two life cycle modes: the latent and lytic phases. KSHV lytic reactivation is known to be important both for viral propagation and for KSHV-induced tumorigenesis. The KSHV replication and transcription activator (RTA) protein is essential for lytic reactivation. Read More

View Article and Full-Text PDF
February 2021

S100A8/S100A9 cytokine acts as a transcriptional coactivator during breast cellular transformation.

Sci Adv 2021 Jan 1;7(1). Epub 2021 Jan 1.

Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School Boston, MA 02115, USA.

Cytokines are extracellular proteins that convey messages between cells by interacting with cognate receptors at the cell surface and triggering signaling pathways that alter gene expression and other phenotypes in an autocrine or paracrine manner. Here, we show that the calcium-dependent cytokines S100A8 and S100A9 are recruited to numerous promoters and enhancers in a model of breast cellular transformation. This recruitment is associated with multiple DNA sequence motifs recognized by DNA binding transcription factors that are linked to transcriptional activation and are important for transformation. Read More

View Article and Full-Text PDF
January 2021

CRISPRi enables isoform-specific loss-of-function screens and identification of gastric cancer-specific isoform dependencies.

Genome Biol 2021 Jan 26;22(1):47. Epub 2021 Jan 26.

Cancer Research Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, 3800, Australia.

Introduction: Genes contain multiple promoters that can drive the expression of various transcript isoforms. Although transcript isoforms from the same gene could have diverse and non-overlapping functions, current loss-of-function methodologies are not able to differentiate between isoform-specific phenotypes.

Results: Here, we show that CRISPR interference (CRISPRi) can be adopted for targeting specific promoters within a gene, enabling isoform-specific loss-of-function genetic screens. Read More

View Article and Full-Text PDF
January 2021

Transcriptional Regulation of PIK3CD and PIKFYVE in T-Cell Acute Lymphoblastic Leukemia by IKAROS and Protein Kinase CK2.

Int J Mol Sci 2021 Jan 15;22(2). Epub 2021 Jan 15.

Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.

IKAROS, encoded by the gene, is a DNA-binding protein that functions as a tumor suppressor in T cell acute lymphoblastic leukemia (T-ALL). Recent studies have identified IKAROS's novel function in the epigenetic regulation of gene expression in T-ALL and uncovered many genes that are likely to be directly regulated by IKAROS. Here, we report the transcriptional regulation of two genes, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta () and phosphoinositide kinase, FYVE-type zinc finger containing (), by IKAROS in T-ALL. Read More

View Article and Full-Text PDF
January 2021

Oncogenic HPV promotes the expression of the long noncoding RNA lnc-FANCI-2 through E7 and YY1.

Proc Natl Acad Sci U S A 2021 01;118(3)

Tumor Virus RNA Biology Section, HIV Dynamics and Replication Program, National Cancer Institute, National Institutes of Health, Frederick, MD 21702;

Long noncoding RNAs (lncRNAs) play diverse roles in biological processes, but their expression profiles and functions in cervical carcinogenesis remain unknown. By RNA-sequencing (RNA-seq) analyses of 18 clinical specimens and selective validation by RT-qPCR analyses of 72 clinical samples, we provide evidence that, relative to normal cervical tissues, 194 lncRNAs are differentially regulated in high-risk (HR)-HPV infection along with cervical lesion progression. One such lncRNA, , is extensively characterized because it is expressed from a genomic locus adjacent to the gene encoding an important DNA repair factor. Read More

View Article and Full-Text PDF
January 2021

L. (Sumac) Demonstrates Oncostatic Activity in the Therapeutic and Preventive Model of Breast Carcinoma.

Int J Mol Sci 2020 Dec 26;22(1). Epub 2020 Dec 26.

Department of Pharmacology, Faculty of Medicine, P. J. Šafárik University, 040 11 Košice, Slovakia.

Comprehensive scientific data provide evidence that isolated phytochemicals or whole plant foods may beneficially modify carcinogenesis. The aim of this study was to evaluate the oncostatic activities of L. (sumac) using animal models (rat and mouse), and cell lines of breast carcinoma. Read More

View Article and Full-Text PDF
December 2020

Long noncoding RNA ATB promotes ovarian cancer tumorigenesis by mediating histone H3 lysine 27 trimethylation through binding to EZH2.

Authors:
Xue-Juan Chen Na An

J Cell Mol Med 2021 Jan 18;25(1):37-46. Epub 2020 Dec 18.

Department of Gynecology, Shengli Oilfield Central Hospital, Dongying, Shandong, China.

Ovarian cancer (OC) remains one of the most lethal gynecological malignancies. The unfavourable prognosis is mainly due to the lack of early-stage diagnosis, drug resistance and recurrence. Therefore, it needs to investigate the mechanism of OC tumorigenesis and identify effective biomarkers for the clinical diagnosis. Read More

View Article and Full-Text PDF
January 2021

Mithramycin induces promoter reprogramming and differentiation of rhabdoid tumor.

EMBO Mol Med 2021 Feb 17;13(2):e12640. Epub 2020 Dec 17.

Van Andel Research Institute, Grand Rapids, MI, USA.

Rhabdoid tumor (RT) is a pediatric cancer characterized by the inactivation of SMARCB1, a subunit of the SWI/SNF chromatin remodeling complex. Although this deletion is the known oncogenic driver, there are limited effective therapeutic options for these patients. Here we use unbiased screening of cell line panels to identify a heightened sensitivity of rhabdoid tumor to mithramycin and the second-generation analogue EC8042. Read More

View Article and Full-Text PDF
February 2021

The expression, modulation and use of cancer-testis antigens as potential biomarkers for cancer immunotherapy.

Am J Transl Res 2020 15;12(11):7002-7019. Epub 2020 Nov 15.

Department of Respiratory Medicine, The Second Hospital of Jilin University Changchun, P. R. China.

Cancer-testis antigens (CTA) are tumor antigens, present in the germ cells of testes, ovaries and trophoblasts, which undergo deregulated expression in the tumor and malignant cells. CTA genes are either X-linked or autosomal, favourably expressed in spermatogonia and spermatocytes, respectively. CTAs trigger unprompted humoral immunity and immune responses in malignancies, altering tumor cell physiology and neoplastic behaviors. Read More

View Article and Full-Text PDF
November 2020

MITF functions as a tumor suppressor in non-small cell lung cancer beyond the canonically oncogenic role.

Aging (Albany NY) 2020 12 3;13(1):646-674. Epub 2020 Dec 3.

Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan.

Microphthalamia-associated transcription factor (MITF) is a critical mediator in melanocyte differentiation and exerts oncogenic functions in melanoma progression. However, the role of MITF in non-small cell lung cancer (NSCLC) is still unknown. We found that is dominantly expressed in the low-invasive CL1-0 lung adenocarcinoma cells and paired adjacent normal lung tissues. Read More

View Article and Full-Text PDF
December 2020

The ARF tumor suppressor targets PPM1G/PP2Cγ to counteract NF-κB transcription tuning cell survival and the inflammatory response.

Proc Natl Acad Sci U S A 2020 12 7;117(51):32594-32605. Epub 2020 Dec 7.

Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75390;

Inducible transcriptional programs mediate the regulation of key biological processes and organismal functions. Despite their complexity, cells have evolved mechanisms to precisely control gene programs in response to environmental cues to regulate cell fate and maintain normal homeostasis. Upon stimulation with proinflammatory cytokines such as tumor necrosis factor-α (TNF), the master transcriptional regulator nuclear factor (NF)-κB utilizes the PPM1G/PP2Cγ phosphatase as a coactivator to normally induce inflammatory and cell survival programs. Read More

View Article and Full-Text PDF
December 2020

High-risk HPV infection modulates the promoter hypermethylation of APC, SFRP1, and PTEN in cervical cancer patients of North India.

Mol Biol Rep 2020 Dec 23;47(12):9725-9732. Epub 2020 Nov 23.

Department of Genetics, Maharishi Dayanand University, Rohtak, 124001, Haryana, India.

Persistent infection with oncogenic HPV and downregulation of tumor suppressor genes play an essential role in the development and progression of cervical cancer. The present study aimed to identify the promoter methylation status of APC, SFRP1, and PTEN which are important regulators of Wnt pathway and their association with high-risk HPV infection and gene expression. Methylation Specific PCR (MSP) and quantitative reverse transcription PCR (RT-qPCR) were used to detect methylation status and gene expression levels of APC, SFRP1, and PTEN in cervical cancer biopsies (110) and paired non-cancerous biopsies (28). Read More

View Article and Full-Text PDF
December 2020

IOX1 Suppresses Wnt Target Gene Transcription and Colorectal Cancer Tumorigenesis through Inhibition of KDM3 Histone Demethylases.

Mol Cancer Ther 2021 01 17;20(1):191-202. Epub 2020 Nov 17.

Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Richmond, Virginia.

Epigenetic activation of Wnt/β-catenin signaling plays a critical role in Wnt-induced tumorigenesis, notably in colorectal cancers. KDM3 and KDM4 histone demethylases have been reported to promote oncogenic Wnt signaling through demethylation of H3K9 on Wnt target gene promoters and are suggested to be potential therapeutic targets. However, potent inhibitors for these regulators are still not available. Read More

View Article and Full-Text PDF
January 2021

A Notch-Dependent Inflammatory Feedback Circuit between Macrophages and Cancer Cells Regulates Pancreatic Cancer Metastasis.

Cancer Res 2021 01 10;81(1):64-76. Epub 2020 Nov 10.

Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.

Notch activation has been detected in pancreatic ductal adenocarcinoma (PDAC). However, its role in PDAC metastasis remains unknown. In this study, we identify a Notch-dependent feedback circuit between pancreatic cancer cells and macrophages, which contributes to PDAC metastasis. Read More

View Article and Full-Text PDF
January 2021

EWS-FLI1 regulates and cooperates with core regulatory circuitry in Ewing sarcoma.

Nucleic Acids Res 2020 11;48(20):11434-11451

Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.

Core regulatory circuitry (CRC)-dependent transcriptional network is critical for developmental tumors in children and adolescents carrying few gene mutations. However, whether and how CRC contributes to transcription regulation in Ewing sarcoma is unknown. Here, we identify and functionally validate a CRC 'trio' constituted by three transcription factors (TFs): KLF15, TCF4 and NKX2-2, in Ewing sarcoma cells. Read More

View Article and Full-Text PDF
November 2020

LINC00922 regulates epithelial-mesenchymal transition, invasive and migratory capacities in breast cancer through promoting NKD2 methylation.

Cell Signal 2021 Jan 9;77:109808. Epub 2020 Oct 9.

Department of Head and Neck Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250117, PR China. Electronic address:

Breast cancer ranks as the major reason for mortality in women populations, accounting for 23% of all cancer deaths. One in every three Asian women encounters the risk of this cancer in their lifetime. Long intergenic non-coding RNAs (lincRNAs) have emerged as tumor promoters and suppressors. Read More

View Article and Full-Text PDF
January 2021

Frizzled Receptors in Tumors, Focusing on Signaling, Roles, Modulation Mechanisms, and Targeted Therapies.

Oncol Res 2021 Mar 30;28(6):661-674. Epub 2020 Sep 30.

Department of Pathophysiology, College of Basic Medical Science, China Medical UniversityShenyangP.R. China.

Wnt molecules play crucial roles in development and adult homeostasis through their receptors Frizzled proteins (Fzds). Fzds mediate canonical -catenin pathway and various noncanonical -catenin-independent pathways. Aberrant Fzd signaling is involved in many diseases including cancer. Read More

View Article and Full-Text PDF

Activation of CpG-Rich Promoters Mediated by MLL Drives MOZ-Rearranged Leukemia.

Cell Rep 2020 09;32(13):108200

Tsuruoka Metabolomics Laboratory, National Cancer Center, Tsuruoka, Yamagata 997-0052, Japan; Division of Hematological Malignancy, National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045, Japan. Electronic address:

Uncontrolled self-renewal of hematopoietic progenitors induces leukemia. To self-renew, leukemia cells must continuously activate genes that were previously active in their mother cells. Here, we describe the circuitry of a transactivation system responsible for oncogenic self-renewal. Read More

View Article and Full-Text PDF
September 2020

Cancer-specific CTCF binding facilitates oncogenic transcriptional dysregulation.

Genome Biol 2020 09 15;21(1):247. Epub 2020 Sep 15.

Center for Public Health Genomics, University of Virginia School of Medicine, Charlottesville, VA, USA.

Background: The three-dimensional genome organization is critical for gene regulation and can malfunction in diseases like cancer. As a key regulator of genome organization, CCCTC-binding factor (CTCF) has been characterized as a DNA-binding protein with important functions in maintaining the topological structure of chromatin and inducing DNA looping. Among the prolific binding sites in the genome, several events with altered CTCF occupancy have been reported as associated with effects in physiology or disease. Read More

View Article and Full-Text PDF
September 2020

Germline-driven replication repair-deficient high-grade gliomas exhibit unique hypomethylation patterns.

Acta Neuropathol 2020 11 8;140(5):765-776. Epub 2020 Sep 8.

The Royal Children's Hospital, 50 Flemington Rd, Parkville, VIC, 3052, Australia.

Replication repair deficiency (RRD) leading to hypermutation is an important driving mechanism of high-grade glioma (HGG) occurring predominantly in the context of germline mutations in RRD-associated genes. Although HGG presents specific patterns of DNA methylation corresponding to oncogenic mutations, this has not been well studied in replication repair-deficient tumors. We analyzed 51 HGG arising in the background of gene mutations in RRD utilizing either 450 k or 850 k methylation arrays. Read More

View Article and Full-Text PDF
November 2020

FOXC1-mediated LINC00301 facilitates tumor progression and triggers an immune-suppressing microenvironment in non-small cell lung cancer by regulating the HIF1α pathway.

Genome Med 2020 09 2;12(1):77. Epub 2020 Sep 2.

Department of Preventive Medicine, School of Health Sciences, Wuhan University, No.115 Donghu Road, Wuchang District, Wuhan, 430071, Hubei, People's Republic of China.

Background: Long non-coding RNAs (lncRNAs) are extensively intricate in the tumorigenesis and metastasis of various cancer types. Nevertheless, the detailed molecular mechanisms of lncRNA in non-small cell lung cancer (NSCLC) still remain mainly undetermined.

Methods: qPCR was performed to verify LINC00301 expression in NSCLC clinical specimens or cell lines. Read More

View Article and Full-Text PDF
September 2020

High-resolution analysis of Merkel Cell Polyomavirus in Merkel Cell Carcinoma reveals distinct integration patterns and suggests NHEJ and MMBIR as underlying mechanisms.

PLoS Pathog 2020 08 24;16(8):e1008562. Epub 2020 Aug 24.

Institute of Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Merkel Cell Polyomavirus (MCPyV) is the etiological agent of the majority of Merkel Cell Carcinomas (MCC). MCPyV positive MCCs harbor integrated, defective viral genomes that constitutively express viral oncogenes. Which molecular mechanisms promote viral integration, if distinct integration patterns exist, and if integration occurs preferentially at loci with specific chromatin states is unknown. Read More

View Article and Full-Text PDF