ArticleOncoTargets and therapy2020
miR-3609 Decelerates the Clearance of Sorafenib in Hepatocellular Carcinoma Cells by Targeting EPAS-1 and Reducing the Activation of the Pregnane X Receptor Pathway.
Article in OncoTargets and therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 12 citations in OpenAlex.
- TPX2 enhances the transcription factor activation of PXR and enhances the resistance of hepatocellular carcinoma cells to antitumor drugs.Cell death & disease · 2023Article
- EPAS1/HIF-2α Acts as an Unanticipated Tumor-Suppressive Role in Papillary Thyroid Carcinoma.International journal of general medicine · 2023Article
- A cohesin-associated gene score may predict immune checkpoint blockade in hepatocellular carcinoma.FEBS open bio · 2022Article
- Hypermethylation of the Promoter Region of miR-23 Enhances the Metastasis and Proliferation of Multiple Myeloma CellsFrontiers in oncology · 2022Article
- Insights into the critical role of the PXR in preventing carcinogenesis and chemotherapeutic drug resistance.International journal of biological sciences · 2022Review
- Regulation of PXR Function by Coactivator and Corepressor Proteins: Ligand Binding Is Just the Beginning.Cells · 2021Review
- The Role of Non-Coding RNAs in the Sorafenib Resistance of Hepatocellular Carcinoma.Frontiers in oncology · 2021Review
- Hsa-miR-4277 Decelerates the Metabolism or Clearance of Sorafenib in HCC Cells and Enhances the Sensitivity of HCC Cells to Sorafenib by TargetingFrontiers in oncology · 2021Article
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe pregnane X receptor (PXR) not only plays an important role in cellular metabolism processes but also induces the resistance of hepatocellular carcinoma (HCC) cells to molecularly targeted drugs by mediating their metabolism and clearance by these cells. Endothelial PAS domain-containing protein 1 (EPAS-1) acts as a coactivator to regulate the transcription factor activity of PXR. In the present study, a microRNA that potentially targets EPAS-1, namely miR-3609, was identified using the miRDB tool.
methodsThe expression of miR-3609 and EPAS-1 was examined by qPCR. Lentiviral particles containing the full-length sequences of miR-3609 (pri-miR-3609) were prepared. The antitumor effect of antitumor agents was examined by the in vitro and in vivo assays.
resultsThe expression of miR-3609 was negatively correlated with that of EPAS-1 in both HCC clinical specimens and paired non-tumor specimens, and the effect of miR-3609 on the expression of EPAS-1 was confirmed by Western blot experiments. Overexpression of miR-3609 decreased the expression of EPAS-1 and, in turn, repressed the activation of the PXR pathway. miR-3609 decreased the transcription factor activation of PXR, repressed its recruitment to its target gene promoter regions, and decreased the expression of its target genes CYP3A4 and P-GP. In addition, miR-3609 decelerated the metabolism and clearance of sorafenib in HCC cells and enhanced the antitumor effect of sorafenib in HCC cells.
conclusionTherefore, the results indicate that miR-3609 decreases the expression of EPAS-1 and enhances the sensitivity of HCC cells to sorafenib.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.