ArticleClinical cancer research : an official journal of the American Association for Cancer Research2013
A tumorigenic factor interactome connected through tumor suppressor microRNA-198 in human pancreatic cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 1 of them a synthesis that pooled it.
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Who cites it
62 citing papers in PubMed, 1 synthesis or guideline pooled it, 83 citations in OpenAlex.
- Pooled it
- Decoding the role of mesothelin in tumor dynamics and targeted treatment innovations.Molecular biomedicine · 2025Review
- Blocking CCR1Cell communication and signaling : CCS · 2025Article
- Mechanisms and progress of LncRNAs in prostate cancer development and diagnostic therapy.International urology and nephrology · 2025Review
- VCP Promotes Cholangiocarcinoma Development by Mediating BAP1 Ubiquitination-Dependent Degradation.Cancer science · 2025Article
- Review
- POU2F2Scientific reports · 2025Article
- Excess shed mesothelin disrupts pancreatic cancer cell clustering to impair peritoneal colonization.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Article
- Pick-up single-cell proteomic analysis for quantifying up to 3000 proteins in a Mammalian cell.Nature communications · 2024Article
- Comprehensive summary: the role of PBX1 in development and cancers.Frontiers in cell and developmental biology · 2024Review
- Functional and Potential Therapeutic Implication of MicroRNAs in Pancreatic Cancer.International journal of molecular sciences · 2023Review
- Biology of Mesothelin and Clinical Implications: A Review of Existing Literature.World journal of oncology · 2023Review
- Circulating MicroRNAs as Noninvasive Diagnostic and Prognostic Biomarkers in Pancreatic Cancer: A Review.Journal of gastrointestinal cancer · 2023Review
- Microbiome and MicroRNA or Long Non-Coding RNA-Two Modern Approaches to Understanding Pancreatic Ductal Adenocarcinoma.Journal of clinical medicine · 2023Review
- Article
- Nanoparticle-Mediated Therapy with miR-198 Sensitizes Pancreatic Cancer to Gemcitabine Treatment through Downregulation of VCP-Mediated Autophagy.Pharmaceutics · 2023Article
- High Mesothelin expression in pancreatic adenocarcinoma is associated with aggressive tumor features but not prognosis.American journal of cancer research · 2023Article
- Review
- The regulation of PBXs and their emerging role in cancer.Journal of cellular and molecular medicine · 2022Review
2 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
purposeThe majority of pancreatic cancers overexpress mesothelin (MSLN), which contributes to enhanced proliferation, invasion, and migration. However, the MSLN regulatory network is still unclear. Here, we investigated the regulation of a panel of tumorigenic factors and explored the potential of MSLN-regulated miR-198 treatment in vivo. EXPERIMENTAL
designThe expression and functional regulation of the tumorigenic factors MSLN, NF-κB, and the homeobox transcription factors (TF) POU2F2 (OCT-2), Pre-B-cell leukemia homeobox factor 1 (PBX-1), valosin-containing protein (VCP), and miR-198 were studied in pancreatic cancer cell lines, patient tumor samples, and xenograft pancreatic cancer mouse models.
resultsWe found that miR-198 is downregulated in pancreatic cancer and is involved in an intricate reciprocal regulatory loop with MSLN, which represses miR-198 through NF-κB-mediated OCT-2 induction. Furthermore, miR-198 repression leads to overexpression of PBX-1 and VCP. The dysregulated PBX-1/VCP axis leads to increased tumorigenicity. Reconstitution of miR-198 in pancreatic cancer cells results in reduced tumor growth, metastasis, and increased survival through direct targeting MSLN, PBX-1, and VCP. Most interestingly, reduced levels of miR-198 in human tissue samples are associated with upregulation of these tumorigenic factors (MSLN, OCT-2, PBX-1, VCP) and predict poor survival. Reduced miR-198 expression links this tumor network signature and prognosticates poor patient outcome. High miR-198 disrupts the network and predicts better prognosis and increased survival.
conclusionsmiR-198 acts as a central tumor suppressor and modulates the molecular makeup of a critical interactome in pancreatic cancer, indicating a potential prognostic marker signature and the therapeutic potential of attacking this tumorigenic network through a central vantage point.
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Registered trials
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