The Roles of miRNA in Glioblastoma Tumor Cell Communication: Diplomatic and Aggressive Negotiations

• Published in: International journal of molecular sciences Vol. 21; no. 6; p. 1950
• Main Authors: Buruiană, Andrei, Florian, Ștefan Ioan, Florian, Alexandru Ioan, Timiș, Teodora-Larisa, Mihu, Carmen Mihaela, Miclăuș, Maria, Oșan, Sergiu, Hrapșa, Iona, Cataniciu, Radu Constantin, Farcaș, Marius, Șușman, Sergiu
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 12-03-2020; MDPI
• Subjects: Angiogenesis; Astrocytes; Biosynthesis; Brain cancer; Calcium channels (voltage-gated); Cell proliferation; Chemokines; Communication; Cytokines; Endothelial cells; Enzymes; Epidermal growth factor receptors; Extracellular vesicles; Gap junctions; Gene expression; Glioblastoma; Glioma cells; intercellular communication; Macrophages; Microglia; MicroRNAs; miRNA; Monocytes; Mutation; Negotiations; Oligodendrocytes; Physiology; Review; RNA polymerase; Signal transduction; Stat3 protein; Stem cells; tumor microenvironment; Tumor suppressor genes; Tumors; intercellular communication; miRNA; glioblastoma; tumor microenvironment
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21061950

Glioblastoma (GBM) consists of a heterogeneous collection of competing cellular clones which communicate with each other and with the tumor microenvironment (TME). MicroRNAs (miRNAs) present various exchange mechanisms: free miRNA, extracellular vesicles (EVs), or gap junctions (GJs). GBM cells transfer miR-4519 and miR-5096 to astrocytes through GJs. Oligodendrocytes located in the invasion front present high levels of miR-219-5p, miR-219-2-3p, and miR-338-3p, all related to their differentiation. There is a reciprocal exchange between GBM cells and endothelial cells (ECs) as miR-5096 promotes angiogenesis after being transferred into ECs, whereas miR-145-5p acts as a tumor suppressor. In glioma stem cells (GSCs), miR-1587 and miR-3620-5p increase the proliferation and miR-1587 inhibits the hormone receptor co-repressor-1 (
) after EVs transfers. GBM-derived EVs carry miR-21 and miR-451 that are up-taken by microglia and monocytes/macrophages, promoting their proliferation. Macrophages release EVs enriched in miR-21 that are transferred to glioma cells. This bidirectional miR-21 exchange increases STAT3 activity in GBM cells and macrophages, promoting invasion, proliferation, angiogenesis, and resistance to treatment. miR-1238 is upregulated in resistant GBM clones and their EVs, conferring resistance to adjacent cells via the CAV1/EGFR signaling pathway. Decrypting these mechanisms could lead to a better patient stratification and the development of novel target therapies.