Synthetic microRNA targeting glioma-associated antigen-1 protein.
The transcription factor glioma-associated antigen-1 (Gli-1) mediates activation of the sonic hedgehog (Shh) pathway, a process that precedes the transformation of tissue stem cells into cancerous stem cells and that is involved in early and late epithelial tumorigenesis. Hypothesizing that targeting the 3'-untranslated region (3'-UTR) of Gli-1 mRNA would effectively inhibit epithelial tumor cell proliferation, we evaluated several complementary miRNA molecules for their ability to do so. The synthetic miRNAs and corresponding duplex/small temporal RNAs were introduced as 3-nucleotide (nt) loops into GU-rich portions of the 3'UTR Gli-1 sequence. One particular miRNA (miRNA Gli-1-3548) and its corresponding duplex (Duplex 3548) significantly inhibited proliferation of Gli-1+ ovarian (SK-OV-3) and pancreatic (MiaPaCa-2) tumor cells by delaying cell division and activating late apoptosis in MiaPaCa-2 cells. Here, we describe the design of effective miRNA sequences and their applications as anti-gene agents.
Tsuda
Naotake
N
Department of Gynecologic Oncology, Kurume University, Kurume, Japan.
Mine
Takahi
T
Ioannides
Constantin G
CG
Chang
David Z
DZ
D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015870:Gene Expression; D020868:Gene Silencing; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D035683:MicroRNAs / Q000138:chemical synthesis* / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism; D000071676:Zinc Finger Protein GLI1
C400551:GLI1 protein, human; D035683:MicroRNAs; D012333:RNA, Messenger; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1