MIR34A
| MIR34A | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Aliases | MIR34A, MIRN34A, miRNA34A, mir-34, mir-34a, microRNA 34a, MIRN34 microRNA, human | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 611172; GeneCards: MIR34A; OMA:MIR34A - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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| Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
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MicroRNA 34a (miR-34a) is a microRNA that in humans is encoded by the MIR34A gene.[3]
Function
[edit]microRNAs (miRNAs) are short (20–24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding.
The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products.
The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop.
Repair of DNA damage
[edit]Expression of miR-34A is markedly up-regulated in hematopoietic stem cells (HSCs) from mice subjected to ionizing radiation.[4] HSCs that are deficient in miR-34A have decreased expression of genes involved in the DNA repair processes of homologous recombination and non-homologous end joining.[4] These and other findings demonstrate that miR-34A contributes to the survival of HSCs after irradiation.[4]
Clinical relevance
[edit]miR-34a suppresses the gene expression of NAMPT, which encodes nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the nicotinamide adenine dinucleotide (NAD) salvage pathway, resulting in reduced levels of NAD.[5] miR-34a suppression of NAMPT gene expression also reduces levels of sirtuin 1.[5] Aging and obesity increase levels of miR-34a.[5] The pro-inflammatory transcription factor NF-κB (increasingly expressed with obesity and aging)[6] increases miR-34a expression by binding to its promoter region.[7] Inhibition of miR-34a in diet-induced obese mice restored levels of NAMPT and NAD, reducing inflammation and improving glucose tolerance.[8]
miR-34a represses the translation of sirtuin 1 (SIRT1) in liver by binding to the 3′-UTR region of SIRT1 messenger RNA, contributing to metabolic syndrome.[9][10] Downregulation of SIRT1 by miR-34a promotes cellular senescence and inflammation in vascular smooth muscle cells of old mice, similar to reduced SIRT1 in vascular smooth muscle cells in humans.[11] Impaired endothelial-dependent vasorelaxation caused by miR-34a can be ameliorated by SIRT1 overexpression.[11]
References
[edit]- ^ a b c GRCh38: Ensembl release 89: ENSG00000284357 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Entrez Gene: MicroRNA 34a".
- ^ a b c Zeng H, Hu M, Lu Y, Zhang Z, Xu Y, Wang S, et al. (July 2019). "MicroRNA 34a promotes ionizing radiation-induced DNA damage repair in murine hematopoietic stem cells". FASEB Journal. 33 (7): 8138–8147. doi:10.1096/fj.201802639R. PMID 30922079.
- ^ a b c Yaku K, Okabe K, Nakagawa T (2018). "NAD Metabolism: Implications in Aging and Longevity". Ageing Research Reviews. 47: 1–17. doi:10.1016/j.arr.2018.05.006. PMID 29883761. S2CID 47002665.
- ^ Kauppinen A, Suuronen T, Ojala J, Kaarniranta K, Salminen A (2013). "Antagonistic crosstalk between NF-κB and SIRT1 in the regulation of inflammation and metabolic disorders". Cellular Signalling. 25 (10): 1939–1948. doi:10.1016/j.cellsig.2013.06.007. PMID 23770291.
- ^ de Gregorio E, Colell A, Morales A, Marí M (2020). "Relevance of SIRT1-NF-κB Axis as Therapeutic Target to Ameliorate Inflammation in Liver Disease". International Journal of Molecular Sciences. 21 (11): 3858. doi:10.3390/ijms21113858. PMC 7312021. PMID 32485811.
- ^ Garten A, Schuster S, Penke M, Kiess W (2015). "Physiological and pathophysiological roles of NAMPT and NAD metabolism". Nature Reviews Endocrinology. 11 (9): 535–546. doi:10.1038/nrendo.2015.117. PMID 26215259. S2CID 11670137.
- ^ Cantó C, Auwerx J (2012). "Targeting sirtuin 1 to improve metabolism: all you need is NAD(+)?". Pharmacological Reviews. 64 (1): 166–187. doi:10.1124/pr.110.003905. PMC 3616312. PMID 22106091.
- ^ Imai S, Yoshino J (2013). "The importance of NAMPT/NAD/SIRT1 in the systemic regulation of metabolism and ageing". Diabetes, Obesity and Metabolism. 15 (Suppl 3): 26–33. doi:10.1111/dom.12171. PMC 3819727. PMID 24003918.
- ^ a b D'Onofrio N, Servillo L, Balestrieri ML (2018). "SIRT1 and SIRT6 Signaling Pathways in Cardiovascular Disease Protection". Antioxidants & Redox Signaling. 28 (8): 711–732. doi:10.1089/ars.2017.7178. PMC 5824538. PMID 28661724.
Further reading
[edit]- Pang RT, Leung CO, Ye TM, Liu W, Chiu PC, Lam KK, Lee KF, Yeung WS (June 2010). "MicroRNA-34a suppresses invasion through downregulation of Notch1 and Jagged1 in cervical carcinoma and choriocarcinoma cells". Carcinogenesis. 31 (6): 1037–44. doi:10.1093/carcin/bgq066. PMID 20351093.
- Lim LP, Glasner ME, Yekta S, Burge CB, Bartel DP (March 2003). "Vertebrate microRNA genes". Science. 299 (5612): 1540. doi:10.1126/science.1080372. PMID 12624257. S2CID 37750545.
- Zauli G, Voltan R, di Iasio MG, Bosco R, Melloni E, Sana ME, Secchiero P (May 2011). "miR-34a induces the downregulation of both E2F1 and B-Myb oncogenes in leukemic cells". Clinical Cancer Research. 17 (9): 2712–24. doi:10.1158/1078-0432.CCR-10-3244. PMID 21367750.
- Forte E, Salinas RE, Chang C, Zhou T, Linnstaedt SD, Gottwein E, Jacobs C, Jima D, Li QJ, Dave SS, Luftig MA (June 2012). "The Epstein-Barr virus (EBV)-induced tumor suppressor microRNA MiR-34a is growth promoting in EBV-infected B cells". Journal of Virology. 86 (12): 6889–98. doi:10.1128/JVI.07056-11. PMC 3393554. PMID 22496226.
- Navarro F, Gutman D, Meire E, Cáceres M, Rigoutsos I, Bentwich Z, Lieberman J (September 2009). "miR-34a contributes to megakaryocytic differentiation of K562 cells independently of p53". Blood. 114 (10): 2181–92. doi:10.1182/blood-2009-02-205062. PMID 19584398.
- Welch C, Chen Y, Stallings RL (July 2007). "MicroRNA-34a functions as a potential tumor suppressor by inducing apoptosis in neuroblastoma cells". Oncogene. 26 (34): 5017–22. doi:10.1038/sj.onc.1210293. PMID 17297439. S2CID 18158985.
- Siemens H, Jackstadt R, Hünten S, Kaller M, Menssen A, Götz U, Hermeking H (December 2011). "miR-34 and SNAIL form a double-negative feedback loop to regulate epithelial-mesenchymal transitions". Cell Cycle. 10 (24): 4256–71. doi:10.4161/cc.10.24.18552. PMID 22134354.
- Yamamura S, Saini S, Majid S, Hirata H, Ueno K, Deng G, Dahiya R (2012). "MicroRNA-34a modulates c-Myc transcriptional complexes to suppress malignancy in human prostate cancer cells". PLOS ONE. 7 (1): e29722. Bibcode:2012PLoSO...729722Y. doi:10.1371/journal.pone.0029722. PMC 3250472. PMID 22235332.
- Lou WJ, Chen Q, Liu L, Qian C (May 2010). "[miR-34s--a tumor suppression protein p53 highly related microRNA]". Yi Chuan = Hereditas. 32 (5): 423–30. doi:10.3724/SP.J.1005.2010.00423. PMID 20466628.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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