Identification of Circulating miRNAs Differentially Regulated by Opioid Treatment
Emerging evidence demonstrates functional contributions of microRNAs (miRNAs) to μ-opioid receptor (MOR) signaling, but the information so far has been mostly limited to their intracellular regulatory mechanisms. The present study aimed to investigate changes in plasma miRNA profiles elicited by opi...
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| Published in | International Journal of Molecular Sciences Vol. 18; no. 9; p. 1991 |
|---|---|
| Main Authors | , , , |
| Format | Journal Article |
| Language | English |
| Published |
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16.09.2017
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| Online Access | Get full text |
| ISSN | 1422-0067 1661-6596 1422-0067 |
| DOI | 10.3390/ijms18091991 |
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| Abstract | Emerging evidence demonstrates functional contributions of microRNAs (miRNAs) to μ-opioid receptor (MOR) signaling, but the information so far has been mostly limited to their intracellular regulatory mechanisms. The present study aimed to investigate changes in plasma miRNA profiles elicited by opioid treatment in blood samples collected from clinical studies. Healthy male subjects were orally administered with hydromorphone or oxycodone and blood samples were collected at a specified time after the drug treatment. A total of 179 plasma miRNAs were measured using multiplex qRT-PCR. Nine and seventeen miRNAs were commonly upregulated (let-7a-5p, miR-423-3p, miR-199a-3p, miR-146a-5p, miR-23b-3p, miR-24-3p, miR-221-3p, miR-223-3p, and miR-146b-5p) and downregulated (miR-144-3p, miR-215, miR-363-3p, etc.), respectively, following opioid treatment. The MOR signaling-associated miRNAs, namely let-7 family miRNAs (i.e., let-7d-5p, let-7f-5p, let-7c, let-7e-5p), miR-103a-3p, miR-339-3p, miR-146a-5p, miR-23b-3p, miR-23a-3p, and miR-181a-5p, were differentially expressed following drug treatment. These differentially expressed miRNAs are circulating biomarker candidates that can be used to evaluate MOR stimulation and serve as novel clinical diagnostic tools for improving clinical outcomes. |
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| AbstractList | Emerging evidence demonstrates functional contributions of microRNAs (miRNAs) to μ-opioid receptor (MOR) signaling, but the information so far has been mostly limited to their intracellular regulatory mechanisms. The present study aimed to investigate changes in plasma miRNA profiles elicited by opioid treatment in blood samples collected from clinical studies. Healthy male subjects were orally administered with hydromorphone or oxycodone and blood samples were collected at a specified time after the drug treatment. A total of 179 plasma miRNAs were measured using multiplex qRT-PCR. Nine and seventeen miRNAs were commonly upregulated (let-7a-5p, miR-423-3p, miR-199a-3p, miR-146a-5p, miR-23b-3p, miR-24-3p, miR-221-3p, miR-223-3p, and miR-146b-5p) and downregulated (miR-144-3p, miR-215, miR-363-3p, etc.), respectively, following opioid treatment. The MOR signaling-associated miRNAs, namely let-7 family miRNAs (i.e., let-7d-5p, let-7f-5p, let-7c, let-7e-5p), miR-103a-3p, miR-339-3p, miR-146a-5p, miR-23b-3p, miR-23a-3p, and miR-181a-5p, were differentially expressed following drug treatment. These differentially expressed miRNAs are circulating biomarker candidates that can be used to evaluate MOR stimulation and serve as novel clinical diagnostic tools for improving clinical outcomes. Emerging evidence demonstrates functional contributions of microRNAs (miRNAs) to μ-opioid receptor (MOR) signaling, but the information so far has been mostly limited to their intracellular regulatory mechanisms. The present study aimed to investigate changes in plasma miRNA profiles elicited by opioid treatment in blood samples collected from clinical studies. Healthy male subjects were orally administered with hydromorphone or oxycodone and blood samples were collected at a specified time after the drug treatment. A total of 179 plasma miRNAs were measured using multiplex qRT-PCR. Nine and seventeen miRNAs were commonly upregulated (let-7a-5p, miR-423-3p, miR-199a-3p, miR-146a-5p, miR-23b-3p, miR-24-3p, miR-221-3p, miR-223-3p, and miR-146b-5p) and downregulated (miR-144-3p, miR-215, miR-363-3p, etc.), respectively, following opioid treatment. The MOR signaling-associated miRNAs, namely let-7 family miRNAs (i.e., let-7d-5p, let-7f-5p, let-7c, let-7e-5p), miR-103a-3p, miR-339-3p, miR-146a-5p, miR-23b-3p, miR-23a-3p, and miR-181a-5p, were differentially expressed following drug treatment. These differentially expressed miRNAs are circulating biomarker candidates that can be used to evaluate MOR stimulation and serve as novel clinical diagnostic tools for improving clinical outcomes.Emerging evidence demonstrates functional contributions of microRNAs (miRNAs) to μ-opioid receptor (MOR) signaling, but the information so far has been mostly limited to their intracellular regulatory mechanisms. The present study aimed to investigate changes in plasma miRNA profiles elicited by opioid treatment in blood samples collected from clinical studies. Healthy male subjects were orally administered with hydromorphone or oxycodone and blood samples were collected at a specified time after the drug treatment. A total of 179 plasma miRNAs were measured using multiplex qRT-PCR. Nine and seventeen miRNAs were commonly upregulated (let-7a-5p, miR-423-3p, miR-199a-3p, miR-146a-5p, miR-23b-3p, miR-24-3p, miR-221-3p, miR-223-3p, and miR-146b-5p) and downregulated (miR-144-3p, miR-215, miR-363-3p, etc.), respectively, following opioid treatment. The MOR signaling-associated miRNAs, namely let-7 family miRNAs (i.e., let-7d-5p, let-7f-5p, let-7c, let-7e-5p), miR-103a-3p, miR-339-3p, miR-146a-5p, miR-23b-3p, miR-23a-3p, and miR-181a-5p, were differentially expressed following drug treatment. These differentially expressed miRNAs are circulating biomarker candidates that can be used to evaluate MOR stimulation and serve as novel clinical diagnostic tools for improving clinical outcomes. |
| Author | Kaoru Toyama Naoki Kiyosawa Kenji Watanabe Hitoshi Ishizuka |
| AuthorAffiliation | 2 Biomarker Research Department, Daiichi Sankyo Co., Ltd., 1-2-58, Hiromachi, Shinagawa, Tokyo 140-8710, Japan; watanabe.kenji.rv@daiichisankyo.co.jp 1 Clinical Pharmacology Department, Daiichi Sankyo Co., Ltd., 1-2-58, Hiromachi, Shinagawa, Tokyo 140-8710, Japan; toyama.kaoru.fb@daiichisankyo.co.jp (K.T.); ishizuka.hitoshi.h8@daiichisankyo.co.jp (H.I.) |
| AuthorAffiliation_xml | – name: 1 Clinical Pharmacology Department, Daiichi Sankyo Co., Ltd., 1-2-58, Hiromachi, Shinagawa, Tokyo 140-8710, Japan; toyama.kaoru.fb@daiichisankyo.co.jp (K.T.); ishizuka.hitoshi.h8@daiichisankyo.co.jp (H.I.) – name: 2 Biomarker Research Department, Daiichi Sankyo Co., Ltd., 1-2-58, Hiromachi, Shinagawa, Tokyo 140-8710, Japan; watanabe.kenji.rv@daiichisankyo.co.jp |
| Author_xml | – sequence: 1 givenname: Kaoru surname: Toyama fullname: Toyama, Kaoru – sequence: 2 givenname: Naoki surname: Kiyosawa fullname: Kiyosawa, Naoki – sequence: 3 givenname: Kenji surname: Watanabe fullname: Watanabe, Kenji – sequence: 4 givenname: Hitoshi surname: Ishizuka fullname: Ishizuka, Hitoshi |
| BackLink | https://cir.nii.ac.jp/crid/1870020693204635776$$DView record in CiNii https://www.ncbi.nlm.nih.gov/pubmed/28926935$$D View this record in MEDLINE/PubMed |
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| Keywords | oxycodone hydromorphone microRNA biomarker μ-opioid receptor qRT-PCR |
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| SubjectTerms | Adult Analgesics, Opioid Analgesics, Opioid - administration & dosage Analgesics, Opioid - pharmacology Biomarkers Biomarkers - blood Fish Humans Hydromorphone Hydromorphone - administration & dosage Hydromorphone - pharmacology hydromorphone; oxycodone; μ-opioid receptor; microRNA; biomarker; qRT-PCR Male MicroRNAs MicroRNAs - blood Narcotics Oxycodone Oxycodone - administration & dosage Oxycodone - pharmacology Receptors, Opioid, mu Receptors, Opioid, mu - drug effects Substance abuse treatment |
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| Title | Identification of Circulating miRNAs Differentially Regulated by Opioid Treatment |
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