MicroRNA-21 Inhibition Enhances In Vitro Chemosensitivity of Temozolomide-resistant Glioblastoma Cells

• Published in: Anticancer research Vol. 32; no. 7; pp. 2835 - 2841
• Main Authors: SZE WONG, Stanley Thian, ZHANG, Xiao-Qin, ZHUANG, James Tin-Fong, CHAN, Hin-Lun, LI, Chi-Han, KIT LEUNG, Gilberto Ka
• Format: Journal Article
• Language: English
• Published: Attiki International Institute of Anticancer Research 01.07.2012
• Subjects: Antineoplastic Agents, Alkylating - pharmacology; Apoptosis; Biological and medical sciences; biomarkers; Biomarkers, Tumor - genetics; Brain Neoplasms - drug therapy; Brain Neoplasms - genetics; Brain Neoplasms - therapy; Brain tumors; Cancer; Cell Line, Tumor; Chemoresistance; Chemotherapy; Combined Modality Therapy; Dacarbazine - analogs & derivatives; Dacarbazine - pharmacology; Genetic Therapy; Glioblastoma - drug therapy; Glioblastoma - genetics; Glioblastoma - therapy; glioblastoma cells; glioblastoma multiforme; Humans; Medical sciences; MicroRNAs - antagonists & inhibitors; MicroRNAs - biosynthesis; MicroRNAs - genetics; miRNA; Neurology; non-coding RNA; Oligonucleotides; Oligonucleotides, Antisense - administration & dosage; Oligonucleotides, Antisense - genetics; temozolomide; Transfection; Tumors; Tumors of the nervous system. Phacomatoses; Antineoplastic agent; Nervous system diseases; Treatment resistance; RNA interference; Glioblastoma; Micro RNA; Malignant tumor; In vitro; Malignant glioma; Gene silencing; Alkylating agent; chemoresistance; Cancerology; MicroRNA; Central nervous system disease; Chemosensitivity; Epigenetics; Inhibitor; Temozolomide; Cancer
• ISSN: 0250-7005; 1791-7530

Glioblastoma multiforme (GBM) is a form of highly malignant brain tumour. Temozolomide (TMZ) is the standard agent for GBM, but TMZ-resistance is common and accounts for many treatment failures. MicroRNA-21 (miR-21) is a non-coding RNA that plays critical roles in many biological processes in cancer, including chemoresistance. We investigated miR-21 expression and the effect of miR-21 inhibition in GBM with acquired TMZ resistance. Human GBM cell line D54MG was treated with TMZ chronically to develop a chemoresistant subclone. MiR-21 inhibition was achieved by transfection with anti-mir-21 oligonucleotide. Chronic TMZ exposure resulted in acquired TMZ-resistance and elevated miR-21 expression. Concomitant treatment with miR-21 inhibitor and TMZ resulted in a significantly higher apoptotic rate than TMZ treatment alone. MiR-21 may have a potential for use as a biomarker of acquired TMZ resistance. MiR-21 inhibition can be further explored as a potential chemotherapy adjunct in the treatment of TMZ-resistant GBM.