MicroRNA, SND1, and alterations in translational regulation in colon carcinogenesis.
Post-transcriptional regulation of gene expression by microRNA (miRNA) has recently attracted major interest in relation to its involvement in cancer development. miRNA is a member of small non-coding RNA, consists of 22-24 nucleotides and regulates expression of target mRNA species in a post-transcriptional manner by being incorporated with RNA-induced silencing complex (RISC). Staphylococcal nuclease homology domain containing 1 (SND1), a component of RISC, is frequently up-regulated in human colon cancers and also chemically induced colon cancers in animals. We here showed that SDN1 is involved in miRNA-mediated gene suppression and overexpression of SND1 in colon cancer cells causes down-regulation of APC without altering APC mRNA levels. As for the miRNA expression profile in human colon cancer, miR-34a was among the list of down-regulated miRNA. Expression of miR-34a is tightly regulated by p53, and ectopic expression of miR-34a in colon cancer cells causes remarkable reduction of cell proliferation and induces senescence-like phenotypes. MiR-34a also participates in the positive feedback loop of the p53 tumor suppressor network. This circuitry mechanism for p53 activation is of interest in understanding the tumor suppressive function of miR-34a in colon carcinogenesis. miRNA should also be considered as novel anti-cancer agents in tumor suppressive therapeutic applications.
Tsuchiya
Naoto
N
Biochemistry Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
Nakagama
Hitoshi
H
D000818:Animals; D003110:Colonic Neoplasms / Q000235:genetics*; D004720:Endonucleases; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism / Q000502:physiology*; D009687:Nuclear Proteins / Q000737:chemistry / Q000502:physiology*; D014176:Protein Biosynthesis; D051153:Wnt Proteins / Q000378:metabolism
C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D009687:Nuclear Proteins; D051153:Wnt Proteins; D004720:Endonucleases; C095221:SND1 protein, human