Targeting MicroRNA-143 Leads to Inhibition of Glioblastoma Tumor Progression

• Published in: Cancers Vol. 10; no. 10; p. 382
• Main Authors: Lozada-Delgado, Eunice L, Grafals-Ruiz, Nilmary, Miranda-Román, Miguel A, Santana-Rivera, Yasmarie, Valiyeva, Fatma, Rivera-Díaz, Mónica, Marcos-Martínez, María J, Vivas-Mejía, Pablo E
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 12-10-2018; MDPI
• Subjects: Animal models; Apoptosis; Brain cancer; Brain tumors; Cancer; Cancer therapies; Cell cycle; Cell growth; Cell proliferation; Cloning; Cyclin-dependent kinases; Diabetes; Gene expression; Glioblastoma; Glucose metabolism; Kinases; Laboratories; Medical prognosis; MicroRNAs; miRNA; Non-coding RNA; Oligonucleotides; Paraffin; Patients; Phase transitions; Polymerase chain reaction; Post-transcription; Protein turnover; Therapeutic applications; Transfection; United States > US; Puerto Rico; microRNAs; glioblastoma; cell proliferation; mouse model
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers10100382

Glioblastoma (GBM) is the most common and aggressive of all brain tumors, with a median survival of only 14 months after initial diagnosis. Novel therapeutic approaches are an unmet need for GBM treatment. MicroRNAs (miRNAs) are a class of small non-coding RNAs that regulate gene expression at the post-transcriptional level. Several dysregulated miRNAs have been identified in all cancer types including GBM. In this study, we aimed to uncover the role of miR-143 in GBM cell lines, patient samples, and mouse models. Quantitative real-time RT-PCR of RNA extracted from formalin-fixed paraffin-embedded (FFPE) samples showed that the relative expression of miR-143 was higher in GBM patients compared to control individuals. Transient transfection of GBM cells with a miR-143 oligonucleotide inhibitor (miR-143-inh) resulted in reduced cell proliferation, increased apoptosis, and cell cycle arrest. SLC30A8, a glucose metabolism-related protein, was identified as a direct target of miR-143 in GBM cells. Moreover, multiple injections of GBM tumor-bearing mice with a miR-143-inh-liposomal formulation significantly reduced tumor growth compared to control mice. The reduced in vitro cell growth and in vivo tumor growth following miRNA-143 inhibition suggests that miR-143 is a potential therapeutic target for GBM therapy.