ArticleCell communication and signaling : CCS2017
MicroRNA-135a regulates NHE9 to inhibit proliferation and migration of glioblastoma cells.
Article in Cell communication and signaling : CCS, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 38 citations in OpenAlex.
- Hsa-miR-25-3p Inhibition Sensitizes Patient-Derived Glioblastoma Cells to Temozolomide via β-catenin Downregulation.Cellular and molecular neurobiology · 2026Article
- MicroRNA-based integrated diagnosis and therapy for GBM: current status and advances.Frontiers in immunology · 2026Review
- Potential for New Therapeutic Approaches by Targeting Lactate and pH Mediated Epigenetic Dysregulation in Major Mental Diseases.Biomedicines · 2024Review
- Tumor-specific polycistronic miRNA delivered by engineered exosomes for the treatment of glioblastoma.Neuro-oncology · 2024Article
- Ion Channels in Gliomas-From Molecular Basis to Treatment.International journal of molecular sciences · 2023Review
- A review on the importance of miRNA-135 in human diseases.Frontiers in genetics · 2022Review
- Gefitinib induces EGFR and α5β1 integrin co-endocytosis in glioblastoma cells.Cellular and molecular life sciences : CMLS · 2021Article
- MicroRNA-183-5p contributes to malignant progression through targeting PDCD4 in human hepatocellular carcinoma.Bioscience reports · 2020Article
- MiR-135a biogenesis and regulation in malignancy: a new hope for cancer research and therapy.Cancer biology & medicine · 2020Review
- MiR-210-3p Inhibits Proliferation and Migration of C6 Cells by Targeting Iscu.Neurochemical research · 2020Article
- Emerging links between endosomal pH and cancer.Cancer metastasis reviews · 2020Review
- miR-135a Alleviates Silica-Induced Pulmonary Fibrosis by Targeting NF-Mediators of inflammation · 2020Article
- A gain of function paradox: Targeted therapy for glioblastoma associated with abnormal NHE9 expression.Journal of cellular and molecular medicine · 2019Article
- Overlapping migratory mechanisms between neural progenitor cells and brain tumor stem cells.Cellular and molecular life sciences : CMLS · 2019Review
- Review
- lncRNA MNX1-AS1 Promotes Glioblastoma Progression Through Inhibition of miR-4443.Oncology research · 2019Article
- Reciprocal regulation of integrin β4 and KLF4 promotes gliomagenesis through maintaining cancer stem cell traits.Journal of experimental & clinical cancer research : CR · 2019Article
- Silencing lncRNA ZFAS1 or elevated microRNA-135a represses proliferation, migration, invasion and resistance to apoptosis of osteosarcoma cells.Cancer cell international · 2019Article
- MicroRNA-652 suppresses malignant phenotypes in glioblastoma multiforme via FOXK1-mediated AKT/mTOR signaling pathway.OncoTargets and therapy · 2019Article
- microRNA-605 directly targets SOX9 to alleviate the aggressive phenotypes of glioblastoma multiforme cell lines by deactivating the PI3K/Akt pathway.OncoTargets and therapy · 2019Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGlioblastoma multiformae (GBM) is the most aggressive type of malignant brain tumor with complex molecular profile. Overexpression of Na
methodsBioinformatics analysis, luciferase reporter assays, real-time PCR and western blotting were conducted to examine the expression profiles and identify microRNAs (miRNA) that target NHE9. Cell proliferation and migration assays were conducted in U87 glioblastoma cells to determine the consequence of miRNA mediated targeting of NHE9. Endosomal pH measurements, immunofluorescence microscopy and surface biotinylation experiments were conducted to characterize the mechanistic basis of regulation.
resultsWe show that microRNA 135a (miR-135a) targets NHE9 to downregulate its expression in U87 cells. MiR-135a levels are significantly lower in glioblastoma cells compared to normal brain tissue. Downregulation of NHE9 expression by miR-135a affects proliferative and migratory capacity of U87 cells. Selectively increasing NHE9 expression in these cells restored their ability to proliferate and migrate. We demonstrate that miR-135a takes a two-pronged approach affecting epidermal growth factor receptors (EGFRs) to suppress tumor cell growth and migration. EGFR activity is a potent stimulator of oncogenic signaling. While miR-135a targets EGFR transcripts to decrease the total number of receptors made, by targeting NHE9 it routes the few EGFRs made away from the plasma membrane to dampen oncogenic signaling. NHE9 is localized to sorting endosomes in glioblastoma cells where it alkalinizes the endosome lumen by leaking protons. Downregulation of NHE9 expression by miR-135a acidifies sorting endosomes limiting EGFR trafficking to the glioblastoma cell membrane.
conclusionsWe propose downregulation of miR-135a as a potential mechanism underlying the high NHE9 expression observed in subset of glioblastomas. Future studies should explore miR-135a as a potential therapeutic for glioblastomas with NHE9 overexpression.
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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 OpenQuestion graph.