INDUSTRY-ACADEMIC COOPERATION FOUNDATION; YONSEI UNIVERSITY
发明人:
KIM, Ho Guen,김호근,KIM, Won Kyu,김원규
申请号：
KRKR2011/001688
公开号：
WO2012/091220A1
申请日:
2011.03.10
申请国别(地区):
WO
年份:
2012
代理人:
摘要：
The present invention relates to a pharmaceutical composition for the prevention or treatment of KIT(v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homologue)-mediated diseases, disorders or conditions, which comprises microRNA-494 (miR-494) or an agent (agents) that induces (induce) miR-494 overexpression. The present invention also relates to a screening method using the pharmaceutical composition. The miR-494 of the present invention binds directly to two different core sequence sites (seed match sites/sequences) in KIT 3-UTR and so effects top-down control of KIT, and reduces the expression of downstream molecules (e.g. phospho-AKT and phospho-STAT3) in the KIT signalling transition pathway, and the miR-494 overexpression induction of the present invention suppresses the growth of neoplastic cells and preferably GIST cell lines. Consequently, when preventing or treating KIT-mediated diseases, disorders or conditions, it is advantageous to use the composition of the present invention which comprises miR-494 and a substance that promotes expression thereof or a substance that suppresses KIT expression of the present invention as an active ingredient.La présente invention concerne une composition pharmaceutique pour la prévention ou le traitement de maladies, troubles ou affections médiés par KIT (homologue de loncogène viral du sarcome félin Hardy-Zuckerman 4 v-kit), qui comprend microARN-494 (miR-494) ou un agent (agents) qui induit (induisent) la surexpression de miR-494. La présente invention concerne en outre un procédé de criblage utilisant la composition pharmaceutique. Le miR-494 de la présente invention se lie directement à deux sites de séquence centrale différents (sites/séquences de correspondance damorce) dans 3-UTR de KIT et effectue donc le contrôle descendant de KIT, et réduit lexpression de molécules en aval (par exemple phospho-AKT et phospho-STAT3) dans la voie de transition de signalisation KIT, et linduction de la surexpression de miR-49
