The Role of TUSC7, a Long Non-Coding-RNA, in Regulating Micro-RNA Mediated Drug Resistance in Glioblastoma
Introduction: Glioblastoma, the most common primary malignant brain tumor in adults, is a debilitating and deadly disease. Currently, standard of care includes maximal surgical resection followed by the Stupp protocol, total 60 Gy over 6 weeks plus temozolomide (TMZ), followed by post-radiation 6 additional cycles of TMZ. Therapy is associated with a 26.5% 2-year-survival rate. The ATP-Binding Cassette Transporter family, consisting of forty-nine proteins are involved in actively transporting numerous substrates, including TMZ out of cancer cells. These efflux proteins, including Multidrug Resistance Protein 1 (MDR1), have long been associated with drug-resistance in GBM. Tumor Suppressor candidate 7 (TUSC7), a long noncoding RNA (lncRNA), expression in GBM cells was recently shown to be negatively correlated with chemo-resistance. Methods: The expression of TUSC7 was detected by quantitative real-time PCR. CCK-8 assay was used to detect cell proliferation ability and chemosensitivity. Flow cytometry was used to detect cell cycle and cell apoptosis. The expression of MDR1 protein was examined by western blot. RNA pull-down assay was applied to confirm the specific combination between TUSC7 and miR-10a. Results: Building on lncRNA data in similar drug efflux trials discussed herein, the paper reviewed in this presentation suggests that the targeting of TUSC7 expression as a mechanism for modifying miRNA10 mediated control of MDR1 expression in GBM is promising and worthy of further research.
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