ArticleInternational journal of cancer2017
miR-130b directly targets ARHGAP1 to drive activation of a metastatic CDC42-PAK1-AP1 positive feedback loop in Ewing sarcoma.
Article in International journal of cancer, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 55 citations in OpenAlex.
- Noncoding RNAs in Pediatric Solid Tumors: Advances in Understanding and Critical Knowledge Gaps.Cells · 2026Review
- CVD phenotyping in oncologic disorders: cardio-miRNAs as a potential target to improve individual outcomes in revers cardio-oncology.Journal of translational medicine · 2024Review
- The Landscape of microRNAs in Bone Tumor: A Comprehensive Review in Recent Studies.MicroRNA (Shariqah, United Arab Emirates) · 2024Review
- Construction of a prognostic risk score model based on the ARHGAP family to predict the survival of osteosarcoma.BMC cancer · 2023Article
- Review
- Molecular and biologic biomarkers of Ewing sarcoma: A systematic review.Journal of bone oncology · 2023Review
- PAK1 overexpression promotes myxofibrosarcoma angiogenesis through STAT5B-mediatedInternational journal of biological sciences · 2023Article
- MiR-130b modulates the invasive, migratory, and metastatic behavior of leiomyosarcoma.PloS one · 2023Article
- High-throughput profiling of histone post-translational modifications and chromatin modifying proteins by reverse phase protein array.Journal of proteomics · 2022Article
- Fixing the GAP: The role of RhoGAPs in cancer.European journal of cell biology · 2022Review
- Article
- MicroRNA Content of Ewing Sarcoma Derived Extracellular Vesicles Leads to Biomarker Potential and Identification of a Previously Undocumented EWS-FLI1 Translocation.Biomarker insights · 2022Article
- The Landscape of Regulatory Noncoding RNAs in Ewing's Sarcoma.Biomedicines · 2021Review
- miR-29a-3p inhibits endometrial cancer cell proliferation, migration and invasion by targeting VEGFA/CD C42/PAK1.BMC cancer · 2021Article
- Novel application of single-cell next-generation sequencing for determination of intratumoral heterogeneity of canine osteosarcoma cell lines.Journal of veterinary diagnostic investigation : official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc · 2021Article
- MicroRNA-130b functions as an oncogene and is a predictive marker of poor prognosis in lung adenocarcinoma.Laboratory investigation; a journal of technical methods and pathology · 2021Article
- p21-activated kinases as viable therapeutic targets for the treatment of high-risk Ewing sarcoma.Oncogene · 2021Article
- Targeting PAK4 Inhibits Ras-Mediated Signaling and Multiple Oncogenic Pathways in High-Risk Rhabdomyosarcoma.Cancer research · 2021Article
- PAK1 and PAK4 as therapeutic targets for Ewing sarcoma: a commentary.Journal of cancer biology · 2021Article
- A novel HDGF-ALCAM axis promotes the metastasis of Ewing sarcoma via regulating the GTPases signaling pathway.Oncogene · 2021Article
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Ewing Sarcoma (ES) is a highly aggressive bone tumor with peak incidence in the adolescent population. It has a high propensity to metastasize, which is associated with dismal survival rates of approximately 25%. To further understand mechanisms of metastasis we investigated microRNA regulatory networks in ES. Our studies focused on miR-130b due to our analysis that enhanced expression of this microRNA has clinical relevance in multiple sarcomas, including ES. Our studies provide insights into a novel positive feedback network involving the direct regulation of miR-130b and activation of downstream signaling events contributing toward sarcoma metastasis. Specifically, we demonstrated miR-130b induces proliferation, invasion, and migration in vitro and increased metastatic potential in vivo. Using microarray analysis of ES cells with differential miR-130b expression we identified alterations in downstream signaling cascades including activation of the CDC42 pathway. We identified ARHGAP1, which is a negative regulator of CDC42, as a novel, direct target of miR-130b. In turn, downstream activation of PAK1 activated the JNK and AP-1 cascades and downstream transcriptional targets including IL-8, MMP1 and CCND1. Furthermore, chromatin immunoprecipitation of endogenous AP-1 in ES cells demonstrated direct binding to an upstream consensus binding site within the miR-130b promoter. Finally, small molecule inhibition of PAK1 blocked miR-130b activation of JNK and downstream AP-1 target genes, including primary miR-130b transcripts, and miR-130b oncogenic properties, thus identifying PAK1 as a novel therapeutic target for ES. Taken together, our findings identify and characterize a novel, targetable miR-130b regulatory network that promotes ES metastasis.
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