title: Using artificial microRNA sponges to achieve microRNA loss-of-function in cancer cells.
abstract: Widely observed dysregulation of microRNAs (miRNAs) in human cancer has led to substantial speculation regarding possible functions of these short, non-coding RNAs in cancer development and manipulation of miRNA expression to treat cancer. To achieve miRNA loss-of-function, miRNA sponge technology has been developed to use plasmid or viral vectors for intracellular expression of tandemly arrayed, bulged miRNA binding sites complementary to a miRNA target to saturate its ability to regulate natural mRNAs. A strong viral promoter can be used in miRNA sponge vectors to generate high-level expression of the competitive inhibitor transcripts for either transient or long-term inhibition of miRNA function. Taking the advantage of sharing a common seed sequence by members of a miRNA family, this technology is especially useful in knocking down the expression of a family of miRNAs, providing a powerful means for simultaneous inhibition of multiple miRNAs of interest with a single inhibitor. Knockdown of overexpressed oncogenic miRNAs with the technology can be a rational therapeutic strategy for cancer, whereas inhibition of tumor-suppressive miRNAs by the sponges will be useful in deciphering functions of miRNAs in oncogenesis. Herein, we discuss the design of miRNA sponge expression vectors and the use of the vectors to gain better understanding of miRNA's roles in cancer biology and as an alternative tool for anticancer gene therapy.
authors.affiliation: Department of Biological Sciences, National University of Singapore, Singapore.
authors.forename: Felix Chang
authors.initials: FC
authors.lastname: Tay
authors.affiliation: Institute of Bioengineering and Nanotechnology, Singapore.
authors.forename: Jia Kai
authors.initials: JK
authors.lastname: Lim
authors.affiliation: Department of Biological Sciences, National University of Singapore, Singapore.
authors.forename: Haibao
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Biological Sciences, National University of Singapore, Singapore.
authors.forename: Lau Cia
authors.initials: LC
authors.lastname: Hin
authors.affiliation: Department of Biological Sciences, National University of Singapore, Singapore; Institute of Bioengineering and Nanotechnology, Singapore. Electronic address: dbsws@nus.edu.sg.
authors.forename: Shu
authors.initials: S
authors.lastname: Wang
mesh_terms: D000818:Animals; D001665:Binding Sites; D055785:Gene Knockdown Techniques; D005822:Genetic Vectors / Q000008:administration & dosage; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics* / Q000628:therapy; D010957:Plasmids; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism*
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger
keywords: Cancer studies; Oncogenic and tumor-suppressive miRNA; Plasmid and viral delivery; miRNA loss-of-function; miRNA sponge