114,436 results match your criteria tyrosine kinases

Gαi1 Promoted Proliferation, Migration and Invasion via Activating the Akt-mTOR/Erk-MAPK Signaling Pathway in Renal Cell Carcinoma.

Onco Targets Ther 2021 4;14:2941-2952. Epub 2021 May 4.

Department of Urology, The Second Affiliated Hospital of Nantong University, Nantong, People's Republic of China.

Background: Renal cell carcinoma (RCC) accounts for about 2-3% of all adult malignancies. G protein alpha inhibitory subunit 1 (Gαi1) plays a key role in mediating PI3K-Akt signaling upon activation of receptor tyrosine kinases (RTKs). However, little is known about its expression, regulation and biological function in RCC. Read More

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A key requirement for synaptic Reelin signaling in ketamine-mediated behavioral and synaptic action.

Proc Natl Acad Sci U S A 2021 May;118(20)

Department of Pharmacology, Vanderbilt University, Nashville, TN 37240-7933;

Ketamine is a noncompetitive -methyl-D-aspartate (NMDA) receptor antagonist that produces rapid antidepressant action in some patients with treatment-resistant depression. However, recent data suggest that ∼50% of patients with treatment-resistant depression do not respond to ketamine. The factors that contribute to the nonresponsiveness to ketamine's antidepressant action remain unclear. Read More

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GlcNAc is a mast-cell chromatin-remodeling oncometabolite that promotes systemic mastocytosis aggressiveness.

Blood 2021 May 11. Epub 2021 May 11.

Centre de Recherche en Cancérologie de Marseille - Inserm U1068, CNRS UMR7258, Aix-Marseille Université, Institut Paoli-Calmettes, Marseille, France.

Systemic mastocytosis (SM) is a KIT-driven hematopoietic neoplasm characterized by the excessive accumulation of neoplastic mast cells (MCs) in various organs and, mainly, the bone marrow (BM). Multiple genetic and epigenetic mechanisms contribute to the onset and severity of SM. However, little is known to date about the metabolic underpinnings underlying SM aggressiveness, which has thus far impeded the development of strategies to leverage metabolic dependencies when existing KIT-targeted treatments fail. Read More

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Lorlatinib Exposure-Response Analyses for Safety and Efficacy in a Phase 1/2 Trial to Support Benefit-Risk Assessment in Non-Small Cell Lung Cancer.

Clin Pharmacol Ther 2021 May 10. Epub 2021 May 10.

Pfizer Inc.

Lorlatinib is a small molecule inhibitor of anaplastic lymphoma kinase (ALK) and c-ROS oncogene 1 (ROS1) tyrosine kinases and is approved for the treatment of patients with ALK-positive advanced non-small cell lung cancer (NSCLC). In the Phase 1/2 study (NCT01970865), potential exposure-response (E-R) relationships between lorlatinib and selected safety and efficacy endpoints were evaluated in patients with NSCLC. E-R relationships were assessed for safety endpoints with incidence >10% in all treated patients (n=328). Read More

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The emerging roles of dual-specificity phosphatases and their specific characteristics in human cancer.

Biochim Biophys Acta Rev Cancer 2021 May 5:188562. Epub 2021 May 5.

Breast and Thyroid Surgery, Southwest Hospital, Army Medical University, Chongqing 400038, China. Electronic address:

Reversible phosphorylation of proteins, controlled by kinases and phosphatases, is involved in various cellular processes. Dual-specificity phosphatases (DUSPs) can dephosphorylate phosphorylated serine, threonine and tyrosine residues. This family consists of 61 members, 44 of which have been identified in human, and these 44 members are classified into six subgroups, the phosphatase and tensin homolog (PTEN) protein phosphatases (PTENs), mitogen-activated protein kinase phosphatases (MKPs), atypical DUSPs, cell division cycle 14 (CDC14) phosphatases (CDC14s), slingshot protein phosphatases (SSHs), and phosphatases of the regenerating liver (PRLs). Read More

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Dasatinib inhibits proliferation of liver cancer cells, but activation of Akt/mTOR compromises dasatinib as a cancer drug.

Acta Biochim Biophys Sin (Shanghai) 2021 May 7. Epub 2021 May 7.

Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan 030001, China.

Dasatinib is a multi-target protein tyrosine kinase inhibitor. Due to its potent inhibition of Src, Abl, the platelet-derived growth factor receptor (PDGFR) family kinases, and other oncogenic kinases, it has been investigated as a targeted therapy for a broad spectrum of cancer types. However, its efficacy has not been significantly extended beyond leukemia. Read More

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LncRNA PINK1-AS promotes Gαi1-driven gastric cancer tumorigenesis by sponging microRNA-200a.

Oncogene 2021 May 6. Epub 2021 May 6.

Center of Translational Medicine, The Affiliated Zhangjiagang Hospital of Soochow University, Suzhou, China.

Gastric cancer (GC) is one of the leading causes of human mortality around the world. We have previously shown that Gαi1 (the inhibitory subunit 1 of the heterotrimeric guanine nucleotide-binding protein) recruitment to ligand-activated receptor tyrosine kinases (RTKs) is essential for signaling. Testing its role in GC cancer-promoting functions, we found that Gαi1 is upregulated in human GC, correlating with poor overall survival. Read More

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Modulation of Akt vs Stat3 activity by the focal adhesion kinase in non-neoplastic mouse fibroblasts.

Exp Cell Res 2021 May 3;404(1):112601. Epub 2021 May 3.

Department of Biomedical and Molecular Sciences and Department of Pathology and Molecular Medicine, Queen's University, Kingston, Ontario, K7L 3N6, Canada.

Adhesion of cells to each other and to the extracellular matrix (ECM) are both required for cellular functions. Cell-to-cell adhesion is mediated by cadherins and their engagement triggers the activation of Stat3, which offers a potent survival signal. Adhesion to the ECM on the other hand, activates FAK which attracts and activates Src, as well as receptor tyrosine kinases (RTKs), the PI3k/Akt and Ras/Erk pathways. Read More

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[Roles of growth factors on vascular remodeling in pulmonary hypertension].

Nihon Yakurigaku Zasshi 2021 ;156(3):161-165

Department of Physiology, Aichi Medical University.

Pulmonary hypertension (PH) is defined as mean pulmonary arterial pressure at rest ≥25 mmHg. Pulmonary arterial hypertension (PAH) is classified as group 1 of PH and is a progressive and fatal disease of the pulmonary artery. The pathogenesis is sustained pulmonary vasoconstriction and pulmonary vascular remodeling, which cause progressive elevations in pulmonary vascular resistance and pulmonary arterial pressure. Read More

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The role of E255K/V-inclusive mutations in a Philadelphia-positive acute lymphoblastic leukemia with mutation evolution during sequential TKIs therapies: A case report.

Medicine (Baltimore) 2021 May;100(18):e25579

Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan.

Rationale: Until recently, the survival rate in patients with Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) was approximately 30%. Tyrosine kinase inhibitors (TKIs), which are a new class of drugs that target BCR-ABL fusion protein, have shown to be effective in treating Ph+ ALL in adults. However, the resistance mechanisms that promote the disease recurrence have altered the initial success of these revolutionary agents. Read More

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Nintedanib attenuates peritoneal fibrosis by inhibiting mesothelial-to-mesenchymal transition, inflammation and angiogenesis.

J Cell Mol Med 2021 May 5. Epub 2021 May 5.

Department of Nephrology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.

Nintedanib, an Food and Drug Administration (FDA) approved multiple tyrosine kinase inhibitor, exhibits an anti-fibrotic effect in lung and kidneys. Its effect on peritoneal fibrosis remains unexplored. In this study, we found that nintedanib administration lessened chlorhexidine gluconate (CG)-induced peritoneal fibrosis and reduced collagen I and fibronectin expression. Read More

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Ripretinib for the treatment of advanced gastrointestinal stromal tumor.

John R Zalcberg

Therap Adv Gastroenterol 2021 15;14:17562848211008177. Epub 2021 Apr 15.

Department of Medical Oncology, Alfred Health and the School of Public Health, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, VIC, Australia.

Gastrointestinal stromal tumors (GISTs) are rare tumors of the gastrointestinal (GI) tract yet represent the most common GI sarcomas. Most GISTs are driven by activating mutations of the and/or genes. Prior to the development of tyrosine kinase inhibitors (TKIs), GISTs were associated with a poor prognosis because conventional cytotoxic chemotherapy was relatively ineffective. Read More

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Structural analysis of the PTEN:P-Rex2 signaling complex reveals how cancer-associated mutations coordinate to hyperactivate Rac1.

Sci Signal 2021 May 4;14(681). Epub 2021 May 4.

Biomedicine Discovery Institute, Monash University, Clayton, 3800 Victoria, Australia.

The dual-specificity phosphatase PTEN functions as a tumor suppressor by hydrolyzing PI(3,4,5)P to PI(4,5)P to inhibit PI3K-AKT signaling and cellular proliferation. P-Rex2 is a guanine nucleotide exchange factor for Rho GTPases and can be activated by Gβγ subunits downstream of G protein-coupled receptor signaling and by PI(3,4,5)P downstream of receptor tyrosine kinases. The PTEN:P-Rex2 complex is a commonly mutated signaling node in metastatic cancer. Read More

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Pharmacological Inhibition of miR-130 Family Suppresses Bladder Tumor Growth by Targeting Various Oncogenic Pathways via PTPN1.

Int J Mol Sci 2021 Apr 29;22(9). Epub 2021 Apr 29.

Laboratory of Molecular and Cellular Physiology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.

Previously, we have revealed that the miR-130 family (miR-130b, miR-301a, and miR-301b) functions as an oncomiR in bladder cancer. The pharmacological inhibition of the miR-130 family molecules by the seed-targeting strategy with an 8-mer tiny locked nucleic acid (LNA) inhibits the growth, migration, and invasion of bladder cancer cells by repressing stress fiber formation. Here, we searched for a functionally advanced target sequence with LNA for the miR-130 family with low cytotoxicity and found LNA #9 (A(L)^i^i^A(L)^T(L)^T(L)^G(L)^5(L)^A(L)^5(L)^T(L)^G) as a candidate LNA. Read More

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Proteolytic Cleavage of Receptor Tyrosine Kinases.

Hao Huang

Biomolecules 2021 Apr 29;11(5). Epub 2021 Apr 29.

Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.

The receptor tyrosine kinases (RTKs) are a large family of cell-surface receptors, which are essential components of signal transduction pathways. There are more than fifty human RTKs that can be grouped into multiple RTK subfamilies. RTKs mediate cellular signaling transduction, and they play important roles in the regulation of numerous cellular processes. Read More

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On-cell nuclear magnetic resonance spectroscopy to probe cell surface interactions.

Biochem Cell Biol 2021 May 4. Epub 2021 May 4.

Dalhousie University, 3688, Department of Biochemistry & Molecular Biology, Halifax, Canada;

Nuclear magnetic resonance (NMR) spectroscopy allows determination of atomic-level information about intermolecular interactions, molecular structure, and molecular dynamics in the cellular environment. This may be broadly divided into studies focused on obtaining detailed molecular information in the intracellular context ("in-cell") or those focused on characterizing molecules or events at the cell surface ("on-cell"). In this review, we outline some key NMR techniques applied for on-cell NMR studies through both solution-state and solid-state NMR and survey studies that have used these techniques to uncover key information. Read More

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Antibody-mediated depletion of CCR10+ EphA3+ cells ameliorates fibrosis in IPF.

JCI Insight 2021 May 4. Epub 2021 May 4.

Division of Pulmonary and Critical Care, Cedars-Sinai Medical Center, Los Angeles, United States of America.

Idiopathic Pulmonary Fibrosis (IPF) is characterized by aberrant repair that diminishes lung function via mechanisms that remain poorly understood. C-C chemokine receptor (CCR10) and its ligand, CCL28, were both elevated in IPF compared with normal donors. CCR10 was highly expressed by various cells from IPF lungs, most notably stage-specific embryonic antigen (SSEA)-4+ mesenchymal progenitor cells (MPCs). Read More

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JAK inhibitors, Psoriatic Arthritis, and Axial Spondyloarthritis: a Critical Review of Clinical Trials.

Expert Rev Clin Immunol 2021 May 4. Epub 2021 May 4.

Division of Rheumatology, University of Alberta, Edmonton, Alberta, Canada.

Introduction: Psoriatic arthritis (PsA) and spondyloarthritis (SpA) are inflammatory arthritides associated with progressive damage, deformity and morbidity. Janus kinase (JAK) inhibitors block JAKs, cytoplasmic protein tyrosine kinases important in signal transduction and immune processes that are currently being studied as synthetic disease modifying anti-rheumatic drugs (tsDMARDs) in psoriatic arthritis and spondyloarthritis.

Areas Covered: This review evaluates published phase 2 and 3 clinical trial data for JAK kinase inhibitors for psoriatic arthritis and spondyloarthritis. Read More

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Identification of EMT signaling cross-talk and gene regulatory networks by single-cell RNA sequencing.

Proc Natl Acad Sci U S A 2021 May;118(19)

Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030;

The epithelial-to-mesenchymal transition (EMT) plays a critical role during normal development and in cancer progression. EMT is induced by various signaling pathways, including TGF-β, BMP, Wnt-β-catenin, NOTCH, Shh, and receptor tyrosine kinases. In this study, we performed single-cell RNA sequencing on MCF10A cells undergoing EMT by TGF-β1 stimulation. Read More

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Protein Serine/Threonine Phosphatase Type 2C of .

Front Cell Infect Microbiol 2021 15;11:641356. Epub 2021 Apr 15.

Unidad de Investigación UNAM-INC, División de Investigación, Facultad de Medicina, Instituto Nacional de Cardiología Ignacio Chávez., Ciudad de México, Mexico.

Protein phosphorylation and dephosphorylation are increasingly recognized as important processes for regulating multiple physiological mechanisms. Phosphorylation is carried out by protein kinases and dephosphorylation by protein phosphatases. Phosphoprotein phosphatases (PPPs), one of three families of protein serine/threonine phosphatases, have great structural diversity and are involved in regulating many cell functions. Read More

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SLAM Associated Protein Signaling in T Cells: Tilting the Balance Toward Autoimmunity.

Front Immunol 2021 16;12:654839. Epub 2021 Apr 16.

Division of Rheumatology, Department of Medicine, Columbia University Irving Medical Center, New York, NY, United States.

T cell activation is the result of the integration of signals across the T cell receptor and adjacent co-receptors. The signaling lymphocyte activation molecules (SLAM) family are transmembrane co-receptors that modulate antigen driven T cell responses. Signal transduction downstream of the SLAM receptor is mediated by the adaptor protein SLAM Associated Protein (SAP), a small intracellular protein with a single SH2 binding domain that can recruit tyrosine kinases as well as shield phosphorylated sites from dephosphorylation. Read More

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Case Report: Reversal of Long-Standing Refractory Diffuse Non-Scarring Alopecia Due to Systemic Lupus Erythematosus Following Treatment With Tofacitinib.

Front Immunol 2021 14;12:654376. Epub 2021 Apr 14.

Department of Rheumatology and Immunology, Shenzhen People's Hospital (The First Affiliated Hospital of Southern University of Science and Technology), The Second Clinical Medical College of Jinan University, Shenzhen, China.

The Janus kinases (JAKs) are intracellular tyrosine kinases involved in a broad variety of inflammatory cascades participating in the pathogenesis of systemic lupus erythematosus (SLE). Diffuse non-scarring alopecia is one of the most frequent cutaneous manifestations in SLE, resulting in devastating psychosocial consequences. Although recent studies have shown promising outcomes of the JAK inhibitors in SLE treatment, the efficacy of tofacitinib in diffuse non-scarring alopecia due to SLE has never been reported. Read More

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Role of FGF System in Neuroendocrine Neoplasms: Potential Therapeutic Applications.

Front Endocrinol (Lausanne) 2021 14;12:665631. Epub 2021 Apr 14.

Department of Clinical Medicine and Surgery, Federico II University of Naples, Naples, Italy.

Neuroendocrine neoplasms (NENs) are a heterogeneous group of tumors originating from neuroendocrine cells dispersed in different organs. Receptor tyrosine kinases are a subclass of tyrosine kinases with a relevant role in several cellular processes including proliferation, differentiation, motility and metabolism. Dysregulation of these receptors is involved in neoplastic development and progression for several tumors, including NENs. Read More

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Discovery of potent and selective reversible Bruton's tyrosine kinase inhibitors.

Bioorg Med Chem 2021 Apr 20;40:116163. Epub 2021 Apr 20.

EMD Serono Research & Development Institute, 45A Middlesex Turnpike, Billerica, MA 01821, USA(1).

Bruton's tyrosine kinase (BTK) is a cytoplasmic, non-receptor tyrosine kinase member of the TEC family of tyrosine kinases. Pre-clinical and clinical data have shown that targeting BTK can be used for the treatment for B-cell disorders. Here we disclose the discovery of a novel imidazo[4,5-b]pyridine series of potent, selective reversible BTK inhibitors through a rational design approach. Read More

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Autophosphorylation and the Dynamics of the Activation of Lck.

Bull Math Biol 2021 May 1;83(6):64. Epub 2021 May 1.

Institut für Mathematik, Johannes Gutenberg-Universität, Staudingerweg 9, 55099, Mainz, Germany.

Lck (lymphocyte-specific protein tyrosine kinase) is an enzyme which plays a number of important roles in the function of immune cells. It belongs to the Src family of kinases which are known to undergo autophosphorylation. It turns out that this leads to a remarkable variety of dynamical behaviour which can occur during their activation. Read More

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Cut-like homeobox 1 (CUX1) tumor suppressor gene haploinsufficiency induces apoptosis evasion to sustain myeloid leukemia.

Nat Commun 2021 04 30;12(1):2482. Epub 2021 Apr 30.

Experimental Cancer Genetics, Wellcome Sanger Institute, Hinxton, UK.

While oncogenes promote tumorigenesis, they also induce deleterious cellular stresses, such as apoptosis, that cancer cells must combat by coopting adaptive responses. Whether tumor suppressor gene haploinsufficiency leads to such phenomena and their mechanistic basis is unclear. Here, we demonstrate that elevated levels of the anti-apoptotic factor, CASP8 and FADD-like apoptosis regulator (CFLAR), promotes apoptosis evasion in acute myeloid leukemia (AML) cells haploinsufficient for the cut-like homeobox 1 (CUX1) transcription factor, whose loss is associated with dismal clinical prognosis. Read More

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Emerging Roles for AKT Isoform Preference in Cancer Progression Pathways.

Mol Cancer Res 2021 Apr 30. Epub 2021 Apr 30.

Cancer Genetics and Genomics, Roswell Park Comprehensive Cancer Center

The phosphoinositol-3 kinase (PI3K)-AKT pathway is one of the most mutated in human cancers, predominantly associated with the loss of the signaling antagonist, PTEN, and to lesser extents, with gain-of-function mutations in PIK3CA (encoding PI3K-p110α) and AKT1. In addition, most oncogenic driver pathways activate PI3K/AKT signaling. Nonetheless, drugs targeting PI3K or AKT have fared poorly against solid tumors in clinical trials as monotherapies, yet some have shown efficacy when combined with inhibitors of other oncogenic drivers, such as receptor tyrosine kinases or nuclear hormone receptors. Read More

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Discovery of a potent and selective Axl inhibitor in preclinical model.

Bioorg Med Chem 2021 Jun 21;39:116137. Epub 2021 Apr 21.

Medicinal Chemistry, Tsukuba Research Laboratories, Eisai Co., Ltd., 5-1-3 Tokodai, Tsukuba-shi, Ibaraki 300-2635, Japan.

Axl and Mer are a members of the TAM (Tyro3-Axl-Mer) family of receptor tyrosine kinases, which, when activated, can promote tumor cell survival, proliferation, migration, invasion, angiogenesis, and tumor-host interactions. Chronic inhibition of Mer leads to retinal toxicity in mice. Therefore, successful development of an Axl targeting agent requires ensuring that it is safe for prolonged treatment. Read More

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DYRK1A Negatively Regulates CDK5-SOX2 Pathway and Self-Renewal of Glioblastoma Stem Cells.

Int J Mol Sci 2021 Apr 13;22(8). Epub 2021 Apr 13.

Charles Perkins Centre and School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia.

Glioblastoma display vast cellular heterogeneity, with glioblastoma stem cells (GSCs) at the apex. The critical role of GSCs in tumour growth and resistance to therapy highlights the need to delineate mechanisms that control stemness and differentiation potential of GSC. Dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) regulates neural progenitor cell differentiation, but its role in cancer stem cell differentiation is largely unknown. Read More

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Long Non-Coding RNA CRNDE Is Involved in Resistance to EGFR Tyrosine Kinase Inhibitor in EGFR-Mutant Lung Cancer via eIF4A3/MUC1/EGFR Signaling.

Int J Mol Sci 2021 Apr 13;22(8). Epub 2021 Apr 13.

Division of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Bunkyo-ku, Tokyo 113-8602, Japan.

(1) Background: Acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is an intractable problem for many clinical oncologists. The mechanisms of resistance to EGFR-TKIs are complex. Long non-coding RNAs (lncRNAs) may play an important role in cancer development and metastasis. Read More

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