title: Double-stranded Let-7 mimics, potential candidates for cancer gene therapy.
abstract: MicroRNAs (miRNAs), a class of small, single-stranded endogenous RNAs, act as post-transcriptional regulators of gene expression. The ability of one single miRNA regulating multiple functionally related mRNAs makes it a new potential candidate for cancer gene therapy. Let-7s miRNAs have been demonstrated as tumor-suppressor genes in various types of cancers, providing one choice of gene therapy by replenishing this miRNA. In the present studies, we demonstrate that the chemically synthesized, double-stranded Let-7 mimics can inhibit the growth and migration and induce the cell cycle arrest of lung cancer cell lines in vitro. Let-7 mimics silence gene expression by binding to the 3' UTR of targeting mRNAs. Mutation of seed sequence significantly depresses the gene silencing activity of Let-7 mimics. Our results also demonstrate that it is possible to increase the activity of Let-7s through mutating the sequence within the 3'end of the antisense strand. Directly, co-transfection Let-7 mimics with active siRNAs impairs the anti-cancer activities of Let-7 mimics. However, a 3-h interval between the introduction of Let-7 mimics and a kind of siRNA avoids the competition and enhances the anti-cancer activities of Let-7 mimics. Taken together, these results have revealed that Let-7s mimics are potential candidates for cancer gene therapy.
authors: Institute of Molecular Medicine, Huaqiao University, Quanzhou, China 362021.
authors: Qi-zhao
authors: QZ
authors: Wang
authors: Ying-hui
authors: YH
authors: Lv
authors: Yu-hua
authors: YH
authors: Gong
authors: Zhao-fa
authors: ZF
authors: Li
authors: William
authors: W
authors: Xu
authors: Yong
authors: Y
authors: Diao
authors: Ruian
authors: R
authors: Xu
mesh_terms: D020413:3' Untranslated Regions; D001483:Base Sequence; D059447:Cell Cycle Checkpoints / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D015316:Genetic Therapy; D006801:Humans; D035683:MicroRNAs / Q000138:chemical synthesis / Q000235:genetics*; D009369:Neoplasms / Q000628:therapy*; D017354:Point Mutation; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D034622:RNA Interference; D012330:RNA, Double-Stranded / Q000138:chemical synthesis / Q000235:genetics*; D014162:Transfection
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; D012330:RNA, Double-Stranded; C487931:mirnlet7 microRNA, human; D016283:Proto-Oncogene Proteins p21(ras)