<i>Retracted:</i> Novel approaches for gene‐specific interference via manipulating actions of microRNAs: Examination on the pacemaker channel genes <i>HCN2</i> and <i>HCN4</i>
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Post-publication record
- Nature
- Retraction
- Reason
- Breach of Policy by Author;Duplication of Data;Duplication of/in Image;Falsification/Fabrication of Data;Investigation by Company/Institution;
- Date
- 11/23/2011 0:00
- Flagged by OpenAlex?
- Yes
Source: Retraction Watch, joined by DOI. OpenAlex records retraction as is_retracted, a boolean over a state space with at least four values, so it cannot express an expression of concern, a correction or a reinstatement — it reports them as false, which reads as “fine”.
Abstract
Recent evidence has suggested microRNAs as viable therapeutic targets for a wide range of human disease. However, lack of gene-specificity of microRNA actions may hinder this application. Here we developed two new approaches, the gene-specific microRNA mimic and microRNA-masking antisense approaches, to explore the possibility of using microRNA's principle of actions in a gene-specific manner. We examined the value of these strategies as rational approaches to develop heart rate-reducing agents and "biological pacemakers" by manipulating the expression of the cardiac pacemaker channel genes HCN2 and HCN4. We showed that the gene-specific microRNA mimics, 22-nt RNAs designed to target the 3'untranslated regions (3'UTRs) of HCN2 and HCN4, respectively, were efficient in abrogating expression and function of HCN2 and HCN4. The gene-specific microRNA mimics repressed protein levels, accompanied by depressed f-channel conductance and the associated rhythmic activity, without affecting mRNA levels of HCN2 and HCN4. Meanwhile, we also designed the microRNA-masking antisense based on the miR-1 and miR-133 target sites in the 3'UTRs of HCN2 and HCN4 and found that these antisense oligodeoxynucleotides markedly enhanced HCN2/HCN4 expression and function, as reflected by increased protein levels of HCN2/HCN4 and If conductance, by removing the repression of HCN2/HCN4 expression induced by endogenous miR-1/miR-133. The experimental examination of these techniques and the resultant findings not only indicate feasibility of interfering miRNA action in a gene-specific fashion but also may provide a new research tool for studying function of miRNAs. The new approaches also have the potential of becoming alternative gene therapy strategies.
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The record
- Venue
- Journal of Cellular Physiology
- Topic
- MicroRNA in disease regulation
- Field
- Biochemistry, Genetics and Molecular Biology
- Canadian institutions
- Université de MontréalMontreal Heart Institute
- Funders
- —
- Keywords
- GenemicroRNAChannel (broadcasting)Computational biologyBiologyInterference (communication)RNA interferenceGeneticsComputer scienceTelecommunicationsRNA
- Has abstract in OpenAlex
- yes