Mir-143 Explained
| mir-143 |
| Width: | 220px |
| Symbol: | mir-143 |
| Rfam: | RF00683 |
| Mirbase Family: | MIPF0000094 |
| Rna Type: | microRNA |
| Tax Domain: | Eukaryota
- Vertebrata
|
| Entrezgene: | 406935 |
| Hgncid: | 31530 |
| Omim: | 612117 |
In molecular biology mir-143 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms. mir–143 is highly conserved in vertebrates. mir-143 is thought be involved in cardiac morphogenesis but has also been implicated in cancer.
Genomic location
mir– 143 is located on chromosome 5 position 33 in the human genome. mir-143 is located very close to mir-145 in the genome and it is speculated that they are transcribed as a bicistronic unit. Their co-transcription means they are frequently studied together in the same cellular pathways and diseases.
Expression
mir–143 is a direct transcriptional target of the serum response factor, myocardin and nkx2-5. mir-143 expression is also thought to be controlled epigenetically through heart beat.
Targets
These are known genetic targets for mir–143 and its effect on them:
- Klf4 – Promotes transcription.
- ELK1 – Promotes transcription.
- ADD3 – Represses transcription. F-actin capping protein.
- FNDC38 – Represses transcription. Tumour metastasis.
- HK2 – Represses transcription. Glucose-6-phosphate catalyzing enzyme.[1]
- Raldh2/aldh1a2 – Represses transcription. Involved in heart tube organization.
- rxrab – Represses transcription. Involved in heart tube organization.
- KLF5 – Unknown has conserved miR – 143 binding site.
- MAP3K7– Unknown has conserved miR – 143 binding site.
- TARDBP – Unknown has conserved miR – 143 binding site.
- UBE2E3– Unknown has conserved miR – 143 binding site.
Cardiogenesis
mir-143 is thought to play an important role in cardiac morphogenesis. mir–143 was found to be the most enriched miRNA in mouse embryonic stem cells that were differentiating into cardiac progenitor cells. It is a direct transcriptional target of serum response factor, myocardin and nkx2-5. Research has shown that mir-143 plays an important role in smooth muscle cell fate. It is co-transcribed with miR-145 in cardiac progenitors before becoming vascular smooth muscle cells (VSMCs). VSMCs are unusual in the fact that they can switch between a proliferative or a quiescent more differentiated state. Along with mir–145, mir- 143 has been shown to target a network of transcription factors (including klf4 and elk-1) that promote differentiation and repress the proliferation of VSMCs.MiR-143 has also been implicated in the more general morphogenesis of the heart. In zebrafish it was shown that mir-143 is required for chamber morphogenesis through repression of add3. A knockout resulted in ventricular collapse. It has also been suggested that mir-143 expression may be controlled by heart beat. In zebrafish mir-143 expression was absent when heartbeat was arrested and restored when heartbeat was reinitiated.Understanding mir– 143 may be important for understanding vascular disease. The plasticity of VSMCs is thought to be the basis of many human vascular diseases such as atherosclerosis.[2] It has also been shown that in human aortic aneurysms the expression of mir-143 and mir-145 were found to be significantly decreased when compared to controls.
Cancer
Changes in mir-143 expression have frequently been implicated in cancer. However the exact nature of this relationship is not fully understood. The up-regulation of mir-143 was observed in a hepatocellular carcinoma model during tumor metastasis through repression of FNDC38. However decreased expression of mir-143 and 145 have been observed in cancer samples. Expression was shown to be decreased in a range of cancer stages, including in very early samples. This suggests that they are involved in tumorgenesis. A modified version of mir-143 (mir-143BP) with greater activity and resistance to nuclease was shown to have a tumor-suppressive effect on colorectal cancer cells. Recent studies with miR-143, in combination with miR-506 has shown to be effective in blocking cell cycle progression of lung cancer cell lines. Moreover, this combination treatment reduces angiogenesis. This makes miR-143 a candidate for RNA medicine for treatment of tumors.
Further reading
- Kulda V, Pesta M, Topolcan O, Liska V, Treska V, Sutnar A, Rupert K, Ludvikova M, Babuska V, Holubec L, Cerny R . Relevance of miR-21 and miR-143 expression in tissue samples of colorectal carcinoma and its liver metastases . Cancer Genet Cytogenet . 200 . 2 . 154–60 . 2010 . 20620599 . 10.1016/j.cancergencyto.2010.04.015.
- Yang Y, Chaerkady R, Kandasamy K, Huang TC, Selvan LD, Dwivedi SB, Kent OA, Mendell JT, Pandey A . Identifying targets of miR-143 using a SILAC-based proteomic approach . Mol Biosyst . 6 . 10 . 1873–82 . 2010 . 20544124 . 10.1039/c004401f. 3812686 .
- Iio A, Nakagawa Y, Hirata I, Naoe T, Akao Y . Identification of non-coding RNAs embracing microRNA-143/145 cluster . Mol Cancer . 9 . 136 . 2010 . 20525177 . 10.1186/1476-4598-9-136 . 2903500 . free .
- Wang X, Hu G, Zhou J . Repression of versican expression by microRNA-143 . J Biol Chem . 285 . 30 . 23241–50 . 2010 . 20489207 . 10.1074/jbc.M109.084673 . 2906317. free .
- Gao W, Yu Y, Cao H, Shen H, Li X, Pan S, Shu Y . Deregulated expression of miR-21, miR-143 and miR-181a in non-small cell lung cancer is related to clinicopathologic characteristics or patient prognosis . Biomed Pharmacother . 64 . 6 . 399–408 . 2010 . 20363096 . 10.1016/j.biopha.2010.01.018.
- Akao Y, Nakagawa Y, Hirata I, Iio A, Itoh T, Kojima K, Nakashima R, Kitade Y, Naoe T . Role of anti-oncomirs miR-143 and -145 in human colorectal tumors . Cancer Gene Ther . 17 . 6 . 398–408 . 2010 . 20094072 . 10.1038/cgt.2009.88. 27389187 .
- Clapé C, Fritz V, Henriquet C, Apparailly F, Fernandez PL, Iborra F, Avancès C, Villalba M, Culine S, Fajas L . miR-143 interferes with ERK5 signaling, and abrogates prostate cancer progression in mice . PLOS ONE . 4 . 10 . e7542 . 2009 . 19855844 . 10.1371/journal.pone.0007542 . 2763222 . Creighton . Chad. free . 2009PLoSO...4.7542C .
- Borralho PM, Kren BT, Castro RE, da Silva IB, Steer CJ, Rodrigues CM . MicroRNA-143 reduces viability and increases sensitivity to 5-fluorouracil in HCT116 human colorectal cancer cells . FEBS J . 276 . 22 . 6689–700 . 2009 . 19843160 . 10.1111/j.1742-4658.2009.07383.x. 205881537 . free .
- Xin M, Small EM, Sutherland LB, Qi X, McAnally J, Plato CF, Richardson JA, Bassel-Duby R, Olson EN . MicroRNAs miR-143 and miR-145 modulate cytoskeletal dynamics and responsiveness of smooth muscle cells to injury . Genes Dev . 23 . 18 . 2166–78 . 2009 . 19720868 . 10.1101/gad.1842409 . 2751981.
- Zhang R, Wang L, Yang AG . Is microRNA-143 really a turncoat of tumor suppressor microRNA in hepatitis B virus-related hepatocellular carcinoma? . Hepatology . 50 . 3 . 987; author reply 987–8 . 2009 . 19670426 . 10.1002/hep.23124. 2177122 . free .
- Ng EK, Tsang WP, Ng SS, Jin HC, Yu J, Li JJ, Röcken C, Ebert MP, Kwok TT, Sung JJ . MicroRNA-143 targets DNA methyltransferases 3A in colorectal cancer . Br J Cancer . 101 . 4 . 699–706 . 2009 . 19638978 . 10.1038/sj.bjc.6605195 . 2736825.
- Zhang X, Liu S, Hu T, Liu S, He Y, Sun S . Up-regulated microRNA-143 transcribed by nuclear factor kappa B enhances hepatocarcinoma metastasis by repressing fibronectin expression . Hepatology . 50 . 2 . 490–9 . 2009 . 19472311 . 10.1002/hep.23008. 32196346 . free .
- Akao Y, Nakagawa Y, Iio A, Naoe T . Role of microRNA-143 in Fas-mediated apoptosis in human T-cell leukemia Jurkat cells . Leuk Res . 33 . 11 . 1530–8 . 2009 . 19464056 . 10.1016/j.leukres.2009.04.019.
Notes and References
- Liu. Pei. Zhu. Lei. Zhang. Fan. Lin. Junhao. Du. Min. Cao. Zilong. Ma. Ling. Hu. Zhensheng. March 2019. LncRNA UCA1/miR-143 miR-216b/HK2/MAPK signaling pathway is involved in the regulation of endothelial cell proliferation via the modulation of glycolysis in melanoma. European Journal of Inflammation. en-US. 17. 1–13. 10.1177/2058739219837050. 2058-7392. free.
- Vacante F, Denby L, Sluimer JC, Baker AH . The function of miR-143, miR-145 and the MiR-143 host gene in cardiovascular development and disease . Vasc Pharmacol . 112 . 24–30 . January 2019 . 30502421 . 6395947 . 10.1016/j.vph.2018.11.006 .
