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MicroRNA‐92b is a potential therapeutic target for Glioblastoma treatment
Author(s) -
GrafalsRuiz Nilmary,
LozadaDelgado Eunice,
SantanaRivera Yasmarie,
RiveraDiaz Monica,
Valiyeva Fatma,
VivasMejía Pablo
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.778.3
Subject(s) - temozolomide , u87 , microrna , cancer research , cell growth , apoptosis , downregulation and upregulation , radioresistance , in vivo , medicine , transfection , cell culture , glioma , radiation therapy , biology , gene , biochemistry , genetics , microbiology and biotechnology
Glioblastoma is the most aggressive type of primary brain tumor with an overall survival of 14.6 months with standard care treatment (surgery, radiotherapy, and Temozolomide chemotherapy). About 90% of patients develop recurrent tumors due to acquired resistance to temozolomide. Therefore, new multimodal treatments that target more than one molecular pathway are needed. MicroRNAs (miRNAs) are small (18–22 nucleotides) non‐coding RNAs that regulate more than 60% of protein coding genes post‐transcriptionally. Their dysregulation is implicated in many diseases including diabetes, heart disease, and cancer. MicroRNA‐92b (miR92b) is highly upregulated in glioblastoma tumors and its expression has an inverse correlation with patient overall survival. This study aims to determine the biological effect of targeting miR92b in glioblastoma. We hypothesized that its inhibition would lead to cell death and decreased proliferation by allowing the expression of messenger RNA (mRNA) targets needed for normal cell function. To determine miR92b targeting effect in vitro , we transfected glioblastoma cell lines with an anti‐miR92b and evaluated cellular apoptosis, clonogenicity, and proliferation. Results showed that by inhibiting miR92b there was an increase in apoptotic cells and reduction of cell proliferation. We next evaluated the miR92b targeting effect in vivo , administering intraperitoneal injections of anti‐miR92b encapsulated liposomes to glioblastoma‐xenograft mice. Inhibiting miR92b in mice xenografts led to a significant decrease in tumor volume and tumor weight. Furthermore, we performed bioinformatic analysis to identify mRNA potential targets of miR92b. We both inhibited and overexpressed miR92b in glioblastoma cells (U87 and CRL1620 respectively) and determined the expression of more than 90 potential mRNA targets by quantitative PCR. This analysis lead to the identification of five potential miR92b mRNA targets‐ASB5, TEF, KIAA1024, ZNF776, FBXW7 and BAZ2‐ which are currently under further validation using Western blot analysis. Our results show that miR92b is a good therapeutic target, since its inhibition leads to increased cell death and decreased cellular proliferation both in vitro and in vivo. MiR92b is a potential target for glioblastoma patients and its targeting could lead to the regulation of tumor suppressive protein coding genes. Support or Funding Information NIGMS‐RISE Grant Number R25‐GM061838, RCMI grant U54 MD007600 (National Institute of Health and Health Disparities), and UPR Comprehensive Center Seed Funds. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .