PMID- 18227514 OWN - NLM STAT- MEDLINE DCOM- 20080307 LR - 20220318 IS - 1091-6490 (Electronic) IS - 0027-8424 (Print) IS - 0027-8424 (Linking) VI - 105 IP - 5 DP - 2008 Feb 5 TI - MicroRNA-373 induces expression of genes with complementary promoter sequences. PG - 1608-13 LID - 10.1073/pnas.0707594105 [doi] AB - Recent studies have shown that microRNA (miRNA) regulates gene expression by repressing translation or directing sequence-specific degradation of complementary mRNA. Here, we report new evidence in which miRNA may also function to induce gene expression. By scanning gene promoters in silico for sequences complementary to known miRNAs, we identified a putative miR-373 target site in the promoter of E-cadherin. Transfection of miR-373 and its precursor hairpin RNA (pre-miR-373) into PC-3 cells readily induced E-cadherin expression. Knockdown experiments confirmed that induction of E-cadherin by pre-miR-373 required the miRNA maturation protein Dicer. Further analysis revealed that cold-shock domain-containing protein C2 (CSDC2), which possesses a putative miR-373 target site within its promoter, was also readily induced in response to miR-373 and pre-miR-373. Furthermore, enrichment of RNA polymerase II was detected at both E-cadherin and CSDC2 promoters after miR-373 transfection. Mismatch mutations to miR-373 indicated that gene induction was specific to the miR-373 sequence. Transfection of promoter-specific dsRNAs revealed that the concurrent induction of E-cadherin and CSDC2 by miR-373 required the miRNA target sites in both promoters. In conclusion, we have identified a miRNA that targets promoter sequences and induces gene expression. These findings reveal a new mode by which miRNAs may regulate gene expression. FAU - Place, Robert F AU - Place RF AD - Department of Urology, Veterans Affairs Medical Center and University of California, San Francisco, CA 94121, USA. place.robert@gmail.com FAU - Li, Long-Cheng AU - Li LC FAU - Pookot, Deepa AU - Pookot D FAU - Noonan, Emily J AU - Noonan EJ FAU - Dahiya, Rajvir AU - Dahiya R LA - eng GR - R01CA101844/CA/NCI NIH HHS/United States GR - R01CA111470/CA/NCI NIH HHS/United States GR - T32DK007790/DK/NIDDK NIH HHS/United States GR - T32 DK007790/DK/NIDDK NIH HHS/United States GR - R01 CA101844/CA/NCI NIH HHS/United States GR - R01 CA111470/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20080128 PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (CSDC2 protein, human) RN - 0 (Cadherins) RN - 0 (MIRN373 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (RNA-Binding Proteins) RN - EC 2.7.7.- (RNA Polymerase II) RN - EC 3.1.26.3 (Ribonuclease III) SB - IM EIN - Proc Natl Acad Sci U S A. 2018 Mar 19;:. PMID: 29555737 MH - Base Pair Mismatch MH - Base Sequence MH - Cadherins/genetics MH - Cell Line, Tumor MH - Gene Expression/drug effects MH - *Gene Expression Regulation MH - Humans MH - MicroRNAs/genetics/pharmacology/*physiology MH - Molecular Sequence Data MH - Promoter Regions, Genetic/drug effects MH - RNA Polymerase II/metabolism MH - RNA-Binding Proteins/genetics MH - Ribonuclease III/antagonists & inhibitors/genetics/metabolism MH - *Transcriptional Activation PMC - PMC2234192 COIS- The authors declare no conflict of interest. EDAT- 2008/01/30 09:00 MHDA- 2008/03/08 09:00 PMCR- 2008/08/05 CRDT- 2008/01/30 09:00 PHST- 2008/01/30 09:00 [pubmed] PHST- 2008/03/08 09:00 [medline] PHST- 2008/01/30 09:00 [entrez] PHST- 2008/08/05 00:00 [pmc-release] AID - 0707594105 [pii] AID - 9140 [pii] AID - 10.1073/pnas.0707594105 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 2008 Feb 5;105(5):1608-13. doi: 10.1073/pnas.0707594105. Epub 2008 Jan 28.