ArticleMolecular cancer2017
Vasohibin 2 reduces chemosensitivity to gemcitabine in pancreatic cancer cells via Jun proto-oncogene dependent transactivation of ribonucleotide reductase regulatory subunit M2.
Article in Molecular cancer, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 28 citations in OpenAlex.
- Bioinformatics Analysis Screening and Identification of Key Biomarkers and Drug Targets in Human Glioblastoma.Current medicinal chemistry · 2025Article
- VASH2 enhances KIF3C-mediated EGFR-endosomal recycling to promote aggression and chemoresistance of lung squamous cell carcinoma by increasing tubulin detyrosination.Cell death & disease · 2024Article
- Chloroxine inhibits pancreatic cancer progression through targeted antagonization of the PI3K/AKT/mTOR signaling pathway.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Article
- Improving the prognosis of pancreatic cancer: insights from epidemiology, genomic alterations, and therapeutic challenges.Frontiers of medicine · 2023Review
- The key cellular senescence related molecule RRM2 regulates prostate cancer progression and resistance to docetaxel treatment.Cell & bioscience · 2023Article
- A preliminary study on the mechanism of VASH2 in childhood medulloblastoma.Scientific reports · 2023Article
- PAK4 inhibition significantly potentiates Gemcitabine activity in PDAC cells via inhibition of Wnt/β-catenin, p-ERK/MAPK and p-AKT/PI3K pathways.Biochemistry and biophysics reports · 2023Article
- Inhibition of JNK/c-Jun-ATF2 Overcomes Cisplatin Resistance in Liver Cancer through down-Regulating Galectin-1.International journal of biological sciences · 2023Article
- HDAC1/3-dependent moderate liquid-liquid phase separation of YY1 promotes METTL3 expression and AML cell proliferation.Cell death & disease · 2022Article
- Still no Rest for the Reductases: Ribonucleotide Reductase (RNR) Structure and Function: An Update.Sub-cellular biochemistry · 2022Review
- Exploration of the System-Level Mechanisms of the Herbal Drug FDY003 for Pancreatic Cancer Treatment: A Network Pharmacological Investigation.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- lncRNAMolecular therapy oncolytics · 2021Article
- Prediction and identification of synergistic compound combinations against pancreatic cancer cells.iScience · 2021Article
- PROM2 promotes gemcitabine chemoresistance via activating the Akt signaling pathway in pancreatic cancer.Experimental & molecular medicine · 2020Article
- VASH2 Promotes Cell Proliferation and Resistance to Doxorubicin in Non-Small Cell Lung Cancer via AKT Signaling.Oncology research · 2020Article
- Knockdown of ribonucleotide reductase regulatory subunit M2 increases the drug sensitivity of chronic myeloid leukemia to imatinib‑based therapy.Oncology reports · 2019Article
- Vasohibin 2 promotes malignant behaviors of pancreatic cancer cells by inducing epithelial-mesenchymal transition via Hedgehog signaling pathway.Cancer medicine · 2018Article
- The Jun/miR-22/HuR regulatory axis contributes to tumourigenesis in colorectal cancer.Molecular cancer · 2018Article
- Requisite role of vasohibin-2 in spontaneous gastric cancer formation and accumulation of cancer-associated fibroblasts.Cancer science · 2017Article
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundVasohibin 2 (VASH2) has previously been identified as an agiogenenic factor and a cancer related protein. Here we investigated the association of VASH2 expression and chemoresistance in pancreatic cancer.
methodsImmunohistochemical staining for VASH2 was performed on 102 human pancreatic cancer samples. Pancreatic cancer cell line models exhibiting overexpression or knockdown of VASH2 were generated. Gene expression analyses were carried out to determine genes differentially regulated by VASH2. Putative transcription factors that are downstream mediators of gene expression regulated by VASH2 were queried bioinformatically. Dual-luciferase reporter assays and ChIP assays were performed to confirm transactivation of target genes following VASH2 overexpression or knockdown.
resultsVASH2 protein expression was higher in human pancreatic cancer than in paired adjacent tissues and elevated VASH2 levels were associated with gemcitabine chemoresistance. In cell line models of pancreatic cancer, VASH2 expression induced gemcitabine chemoresistance in vitro and in vivo. It was discovered that expression of ribonucleotide reductase regulatory subunit M2 (RRM2) is regulated by VASH2; immunohistochemical analysis demonstrated a positive association of VASH2 expression and RRM2 expression in human pancreatic cancer tissues. Bioinformatics analyses revealed that induction of the Jun proto-oncogene (JUN) by VASH2 is responsible for upregulation of RRM2 expression; this JUN-dependent regulation of RRM2 by VASH2 was confirmed by chromatin immunoprecipitation and dual luciferase reporter assays, which demonstrated that JUN directly binds with the RRM2 promoter to activate transcription.
conclusionsThese data suggest that VASH2 reduces the chemosensitivity to gemcitabine in pancreatic cancer cells via JUN-dependent transactivation of RRM2.
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