ArticleJournal of experimental & clinical cancer research : CR2018
Paired box 8 suppresses tumor angiogenesis and metastasis in gastric cancer through repression of FOXM1 via induction of microRNA-612.
Article in Journal of experimental & clinical cancer research : CR, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 27 citations in OpenAlex.
- The role of microRNAs in the gastric cancer tumor microenvironment.Molecular cancer · 2024Review
- Identification of a four-miRNA signature predicts the prognosis of papillary thyroid cancer.World journal of clinical cases · 2023Article
- NEAT1 can be a diagnostic biomarker in the breast cancer and gastric cancer patients by targeting XIST, hsa-miR-612, and MTRNR2L8: integrated RNA targetome interaction and experimental expression analysis.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2022Article
- Enhancer of zeste homolog 2-mediated paired box 8 methylation promotes gastrointestinal stromal tumor progression through Wnt4 downregulation.Cancer gene therapy · 2021Article
- Angiogenesis-related non-coding RNAs and gastrointestinal cancer.Molecular therapy oncolytics · 2021Review
- LncRNA OSER1-AS1 interacts with miR-612/FOXM1 axis to modulate gefitinib resistance of lung adenocarcinoma.American journal of translational research · 2021Article
- Reciprocal Dysregulation of MiR-146b and MiR-451 Contributes in Malignant Phenotype of Follicular Thyroid Tumor.International journal of molecular sciences · 2020Article
- MicroRNA-612 inhibits cervical cancer progression by targeting NOB1.Journal of cellular and molecular medicine · 2020Article
- Review
- HBx regulates transcription factor PAX8 stabilization to promote the progression of hepatocellular carcinoma.Oncogene · 2019Article
- Article
- Based on Integrated Bioinformatics Analysis Identification of Biomarkers in Hepatocellular Carcinoma Patients from Different Regions.BioMed research international · 2019Article
- Gastric Cancer Heterogeneity and Clinical Outcomes.Technology in cancer research & treatmentArticle
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
backgroundPaired box 8 (PAX8) has been documented to be downregulated in gastric cancer. However, its biological function in this malignancy is poorly understood.
methodsIn the present work, we investigated the effects of PAX8 overexpression and knockdown on the aggressive phenotype of gastric cancer cells. We further checked the involvement of forkhead box M1 (FOXM1), a ubiquitously expressed oncogene that can facilitate gastric cancer progression, in the action of PAX8.
resultsEctopic expression of PAX8 blocked the migration and invasion of both AGS and SGC-7901 cells, but had no effect on cell proliferation. Conversely, knockdown of PAX8 enhanced gastric cancer cell migration and invasion. PAX8 overexpression inhibited epithelial-mesenchymal transition (EMT) and pro-angiogenic activity of gastric cancer cells. Mechanistically, PAX8 overexpression downregulated FOXM1 by stimulating microRNA (miR)-612 expression. Ectopic expression of miR-612 recapitulated the effect of PAX8 overexpression on gastric cancer cells, causing an inhibition of migration, invasion, EMT, and angiogenesis. Knockdown of miR-612 or overexpression of FOXM1 significantly reversed the tumor-suppressive activity of PAX8. In vivo studies further demonstrated that PAX8 overexpression restrained tumor angiogenesis and metastasis in nude mice, which was accompanied by increased expression of miR-612 and decreased expression of FOXM1.
conclusionsPAX8 exerts a tumor-suppressive effect against gastric cancer cells, largely through induction of miR-612 and repression of FOXM1. Therefore, restoration of PAX8 expression may offer therapeutic benefits in the treatment of gastric cancer.
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