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ARTICLES Inhibition of Tumor Growth by Ribozyme-Mediated Suppression of Aberrant Epidermal Growth Factor Receptor Gene Expression

By Hitoshi Yamazaki, Hiroshi Kijima, Yasuyuki Ohnishi, Yoshiyuki Abe, Yoshiro Oshika, Takashi Tsuchida, Tetsuji Tokunaga, Atsushi Tsugu, Yoshito Ueyama, Norikazu Tamaoki and Masato Nakamura


Background: Amplification and rearrangement of the epidermal growth factor receptor (EGFR) gene is frequently associated with malignant gliomas. One type of EGFR mutation in primary gliomas results in overexpression of an aberrant EGFR messenger RNA (mRNA) that lacks sequences of exons II through VI of the human EGFR gene. We observed that the aberrantly spliced EGFR mRNA contains a ribozyme cleavable sequence (5�-AAG GUA AUU-3�) created by the joining of EGFR exon I to exon VII. We hypothesized that an appropriately designed ribozyme RNA could mediate site-specific cleavage of the aberrant EGFR mRNA and reduce the growth of aberrant EGFR-producing tumor cells. Methods: We synthesized aberrant EGFR mRNA substrates and a sequence-specific hammerhead ribozyme (abEGFR-rib) to examine the ribozyme’s activit

Year: 2013
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