Abstract
Leucine-rich repeat (LRR) genes encode transmembrane proteins that are essential for normal brain development and are often dysregulated in central nervous system tumors. Leucine-rich repeat C4 (LRRC4) is a member of the LRR protein superfamily and specifically expressed in brain tissue. Importantly it acts as a tumor suppressor in the pathogenesis of malignant gliomas. However, the molecular mechanisms by which LRRC4 regulates glioma tumorigenesis are largely unknown. In this report, we found that miR-185 is markedly upregulated by LRRC4. We also found that miR-185 was downregulated in glioma, and overexpression of miR-185 inhibited glioma cell invasion. Low expressions of LRRC4 and miR-185 were associated with a poor outcome in glioma patients. Further investigation revealed that LRRC4 mediated its tumor suppressor function by regulating miR-185 targets CDC42 and RhoA. LRRC4 overexpression inhibited glioma cell invasion through miR-185-mediated CDC42 and RhoA direct regulation and VEGFA indirect regulation. Together, our findings suggest that the altered expression of the tumor suppressor LRRC4 may be an important event that leads to the dysregulation of miR-185 in human gliomas. LRRC4 and miR-185 may also be good prognostic markers and therapeutic targets in glioma.
Current Cancer Drug Targets
Title:LRRC4 Inhibits Glioma Cell Growth and Invasion Through a miR-185- Dependent Pathway
Volume: 12 Issue: 8
Author(s): Hailin Tang, Zeyou Wang, Xiaoping Liu, Qing Liu, Gang Xu, Guiyuan Li and Minghua Wu
Affiliation:
Keywords: CDC42, glioma, invasion, LRRC4, miRNA, RhoA
Abstract: Leucine-rich repeat (LRR) genes encode transmembrane proteins that are essential for normal brain development and are often dysregulated in central nervous system tumors. Leucine-rich repeat C4 (LRRC4) is a member of the LRR protein superfamily and specifically expressed in brain tissue. Importantly it acts as a tumor suppressor in the pathogenesis of malignant gliomas. However, the molecular mechanisms by which LRRC4 regulates glioma tumorigenesis are largely unknown. In this report, we found that miR-185 is markedly upregulated by LRRC4. We also found that miR-185 was downregulated in glioma, and overexpression of miR-185 inhibited glioma cell invasion. Low expressions of LRRC4 and miR-185 were associated with a poor outcome in glioma patients. Further investigation revealed that LRRC4 mediated its tumor suppressor function by regulating miR-185 targets CDC42 and RhoA. LRRC4 overexpression inhibited glioma cell invasion through miR-185-mediated CDC42 and RhoA direct regulation and VEGFA indirect regulation. Together, our findings suggest that the altered expression of the tumor suppressor LRRC4 may be an important event that leads to the dysregulation of miR-185 in human gliomas. LRRC4 and miR-185 may also be good prognostic markers and therapeutic targets in glioma.
Export Options
About this article
Cite this article as:
Tang Hailin, Wang Zeyou, Liu Xiaoping, Liu Qing, Xu Gang, Li Guiyuan and Wu Minghua, LRRC4 Inhibits Glioma Cell Growth and Invasion Through a miR-185- Dependent Pathway, Current Cancer Drug Targets 2012; 12 (8) . https://dx.doi.org/10.2174/156800912803251180
DOI https://dx.doi.org/10.2174/156800912803251180 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
Call for Papers in Thematic Issues
Advances in Cancer Biomarkers and Potential Drug Targets: From Diagnosis to Therapy
Cancer biomarkers play a crucial role in the diagnosis, prognosis, and treatment of cancer. They provide valuable information for cancer detection, risk assessment, treatment selection, and monitoring response to therapy. With advancements in molecular biology and high-throughput technologies, there has been an increasing interest in identifying and characterizing cancer biomarkers ...read more
Novel Therapeutic Approaches to Target Drug Resistant Tumors
With the development of disciplines such as chemical biology and molecular biology, the genes or proteins closely related to tumor occurrence and development have gradually become clear. Targeted therapies targeting these genes or proteins provide more effective methods for tumor treatment. Tumor targeted drugs generally only act on specific targets ...read more
ROLE OF IMMUNE AND GENOTOXIC RESPONSE BIOMARKERS IN TUMOR MICROENVIRONMENT IN CANCER DIAGNOSIS AND TREATMENT
Biological biomarkers have been used in medical research as an indicator of a normal or abnormal process inside the body, or of a disease. Nowadays, various researchers are in process to explore and investigate the biological markers for the early assessment of cancer. DNA Damage response (DDR) pathways and immune ...read more
Targeting the battlefield between host and tumor: basic research and clinical practice on reshaping tumor immune microenvironment
Immune system protects host against malignant tumors through effector cells and molecules. Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses cancer progression. Chronic inflammation facilitates cancer progression and treatment resistance, whereas induction of acute inflammatory reactions often lead to anti-cancer immune responses. ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Cancer Stem Cells Equipped with Powerful Hedgehog Signaling and Better Epigenetic Memory: Avenues to Look for Cancer Therapeutics
Current Cancer Drug Targets Aptamers: Potential Applications to Pancreatic Cancer Therapy
Anti-Cancer Agents in Medicinal Chemistry Isoflavones, their Glycosides and Glycoconjugates. Synthesis and Biological Activity
Current Organic Chemistry Modulation of Tumour-Related Signaling Pathways by Natural Pentacyclic Triterpenoids and their Semisynthetic Derivatives
Current Medicinal Chemistry Anti-Epidermal Growth Factor Receptor Antibodies in the Treatment of Metastatic Colorectal Cancer
Recent Patents on Anti-Cancer Drug Discovery Pathophysiological Role of Mitochondrial Potassium Channels and their Modulation by Drugs
Current Medicinal Chemistry Apoptosis and Autophagy Induction As Mechanism of Cancer Prevention by Naturally Occurring Dietary Agents
Current Drug Targets What Makes Y Family Pols Potential Candidates for Molecular Targeted Therapies and Novel Biotechnological Applications
Current Molecular Medicine Selectively Replicating Adenoviruses for Oncolytic Therapy
Current Cancer Drug Targets Progress of HDAC Inhibitor Panobinostat in the Treatment of Cancer
Current Drug Targets Considering Autotaxin Inhibitors in Terms of 2D-QSAR and 3D-Mapping- Review and Evaluation
Current Medicinal Chemistry Oxidovanadium(IV) Complex Disrupts Mitochondrial Membrane Potential and Induces Apoptosis in Pancreatic Cancer Cells
Anti-Cancer Agents in Medicinal Chemistry Pregabalin in Neuropathic Pain: Evidences and Possible Mechanisms
Current Neuropharmacology Blockade of Insulin-Like Growth Factor Type-1 Receptor with Cixutumumab (IMC-A12): A Novel Approach to Treatment for Multiple Cancers
Current Drug Targets Nanoprobes for Medical Diagnosis: Current Status of Nanotechnology in Molecular Imaging
Current Nanoscience FOXM1 and its Oncogenic Signaling in Gastric Cancer
Recent Patents on Anti-Cancer Drug Discovery Arsenic Trioxide and Artemisinin Act Synergistically to Kill Tumor Cells In Vitro
Anti-Cancer Agents in Medicinal Chemistry Targeting Epidermal Growth Factor Receptor in Solid Tumors: Critical Evaluation of the Biological Importance of Therapeutic Monoclonal Antibodies
Current Medicinal Chemistry Cross Talk between the Cardiovascular and Nervous Systems:Neurotrophic Effects of Vascular Endothelial Growth Factor (VEGF) and Angiogenic Effects of Nerve Growth Factor (NGF)-Implications in Drug Development
Current Pharmaceutical Design Recent Patents of Gene Sequences Relative to the Phosphatidylinositol 3-kinase / Akt Pathway and their Relevance to Drug Discovery
Recent Patents on DNA & Gene Sequences