Unlabelled: Increasing evidence supports a role for N-myc downstream-regulated gene 2 (NDRG2) deregulation in tumorigenesis. We investigated the roles and mechanisms of NDRG2 in human cholangiocarcinoma (CCA) progression. In the present study, expression of NDRG2, microRNA (miR)-181c and leukemia inhibitory factor (LIF) in human CCA and adjacent nontumor tissues were examined. The effects of NDRG2 on CCA tumor growth and metastasis were determined both in vivo and in vitro. The role of the NDRG2/LIF/miR-181c signaling pathway in cholangiocarcinogenesis and metastasis were investigated both in vivo and in vitro. The results showed that human CCA tissues exhibited decreased levels of NDRG2 and increased levels of miR-181c and LIF compared with nontumor tissues. NDRG2 could inhibit CCA cell proliferation, chemoresistance, and metastasis both in vitro and in vivo. We found that NDRG2 is a target gene of miR-181c, and the down-regulation of NDRG2 was attributed to miR-181c overexpression in CCA. Furthermore, miR-181c can be activated by LIF treatment, whereas NDRG2 could inhibit LIF transcription through disrupting the binding between Smad, small mothers against decapentaplegic complex and LIF promoter. Down-regulation of NDRG2 and overexpression of miR-181c or LIF are significantly associated with a poorer overall survival (OS) in CCA patients. Finally, we found that a combination of NDRG2, miR-181c, and LIF expression is a strong predictor of prognosis in CCA patients.
Conclusion: These results establish the counteraction between NDRG2 and LIF/miR-181c as a key mechanism that regulates cholangiocarcinogenesis and metastasis. Our results elucidated a novel pathway in NDRG2-mediated inhibition of cholangiocarcinogenesis and metastasis and suggest new therapeutic targets, including NDRG2, LIF, miR-181c, and transforming growth factor beta, in CCA prevention and treatment. (Hepatology 2016;64:1606-1622).
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/hep.28781 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Gamma-aminobutyric acid-mediated neuro-immune interactions in glioblastoma: Implications for prognosis and immunotherapy response.
Life Sci
November 2024
Department of Neurosurgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China. Electronic address:
Aims: This study aimed to investigate the role of gamma-aminobutyric acid (GABA) in the glioblastoma (GBM) tumor immune microenvironment (TIME) and its impact on prognosis and response to immunotherapy.
Main Methods: This study employed single-cell RNA sequencing (scRNA-seq) to delineate the TIME of GBM, utilized non-negative matrix factorization (NMF) for GABA-associated cell clustering, and performed pseudotime analysis for cellular trajectories. Additionally, we integrated immunohistochemistry (IHC), immunofluorescence (IF), and protein-protein interaction (PPI) analysis to explore the regulatory mechanisms within the tumor microenvironment.
From bioinformatics to clinical applications: a novel prognostic model of cuproptosis-related genes based on single-cell RNA sequencing data in hepatocellular carcinoma.
BMC Immunol
September 2024
Department of Pathology, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin's Clinical Research Center for Cancer, Huanhuxi Road, Hexi District, Tianjin, Tianjin, 300060, China.
Objective And Methods: To ascertain the connection between cuproptosis-related genes (CRGs) and the prognosis of hepatocellular carcinoma (HCC) via single-cell RNA sequencing (scRNA-seq) and RNA sequencing (RNA-seq) data, relevant data were downloaded from the GEO and TCGA databases. The differentially expressed CRGs (DE-CRGs) were filtered by the overlaps in differentially expressed genes (DEGs) between HCC patients and normal controls (NCs) in the scRNA-seq database, DE-CRGs between high- and low-CRG-activity cells, and DEGs between HCC patients and NCs in the TCGA database.
Results: Thirty-three DE-CRGs in HCC were identified.
NDRG2 regulates glucose metabolism and ferroptosis of OGD/R-treated astrocytes by the Wnt/β-catenin signaling.
J Biochem Mol Toxicol
September 2024
Department of Neurosurgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, China.
Ischemic stroke is one main type of cerebrovascular disorders with leading cause of death and disability worldwide. Astrocytes are the only nerve cell type storing glycogen in the brain, which regulate the glucose metabolism and handle the energy supply and survive of neurons. Astrocyte ferroptosis contributes to neuron injury in brain disorders.
View Article and Find Full Text PDFNDRG2 Deficiency Exacerbates UVB-Induced Skin Inflammation and Oxidative Stress Damage.
Inflammation
August 2024
Department of Plastic and Reconstructive Surgery, Senior Department of Burn and Plastic Surgery, The Fourth Medical Center of Chinese, PLA General Hospital and PLA Medical College, Beijing, 100048, China.
UVB radiation induces inflammatory and oxidative stress responses, contributing to skin damage, yet the underlying mechanisms are not fully understood. N-Myc downstream-regulated gene 2 (NDRG2), an emerging stress-associated gene, remains unexplored in UVB-induced skin injury. In this study, we detected skin NDRG2 expression after UVB irradiation for the first time and further used Ndrg2 knockout mice to clarify the role of NDRG2 in UVB-induced skin injury.
View Article and Find Full Text PDFIntegrative analyses of genes associated with oxidative stress and cellular senescence in triple-negative breast cancer.
Heliyon
July 2024
Department of Pathology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China.
Background: Oxidative stress and cellular senescence (OSCS) have great impacts on the occurrence and progression of triple-negative breast cancer (TNBC). This study was intended to construct a prognostic model based on oxidative stress and cellular senescence related difference expression genes (OSCSRDEGs) for TNBC.
Methods: The Cancer Genome Atlas (TCGA) databases and two Gene Expression Omnibus (GEO) databases were used to identify OSCSRDEGs.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!