miR-139-5p modulates cortical neuronal migration by targeting Lis1 in a rat model of focal cortical dysplasia

Huang,Yanjun; Jiang,Jiao; Zheng,Guo; Chen,Jing; Lu,Haiying; Guo,Hu; Wu,Chunfeng

doi:10.3892/ijmm.2014.1703

miR-139-5p modulates cortical neuronal migration by targeting Lis1 in a rat model of focal cortical dysplasia

Authors:
- Yanjun Huang
- Jiao Jiang
- Guo Zheng
- Jing Chen
- Haiying Lu
- Hu Guo
- Chunfeng Wu
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Affiliations: Department of Neurology, Nanjing Children's Hospital, Nanjing Medical University, Nanjing, Jiangsu 210008, P.R. China
Published online on: March 18, 2014 https://doi.org/10.3892/ijmm.2014.1703
Pages: 1407-1414
Copyright: © Huang et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Accumulating evidence has indicated that microRNAs (miRNAs or miRs) play important roles in the developing rat brain. In this study, we investigated the role of miRNAs in the brains of immature (20-80 days) rats with liquid nitrogen lesion-induced focal cortical dysplasia. miRNA microarray demonstrated that the expression of miR-139‑5p was associated with cortical development. Bioinformatic analysis and luciferase assays revealed that the Lis1 gene is a likely target of miR-139‑5p. It is known that Lis1 plays a role in cell proliferation and migration and can lead to cortical dysplasia when mutated. Our data demonstrated an inhibitory effect of miR-139-5p on the expression of Lis1 in PC12 cells 24 h following transfection with pre-miR-139-5p. However, when the PC12 cells were transfected with anti-miR-139-5p, an increase was observed in the expression of Lis1. Cell migration assay revealed that miR-139-5p significantly inhibited the migration of PC12 and HCN-2 cells treated with or without Lis1 protein. In addition, a rat model of focal cortical dysplasia was established, wherein miR-139-5p was administered and Lis1 expression was found to be markedly reduced. Moreover, the injured cortex showed a certain degree of recovery following the administration of miR‑139-5p, demonstrating that the reduction in miR-139-5p was at least partially responsible for the upregulation of Lis1 in the rat brains. Our data suggest that miR-139-5p modulates cortical neuronal migration by targeting Lis1.

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1	Barkovich AJ, Kuzniecky RI, Jackson GD, Guerrini R and Dobyns WB: A developmental and genetic classification for malformations of cortical development. Neurology. 65:1873–1887. 2005. View Article : Google Scholar : PubMed/NCBI
2	Andiman E, Haynes L, Trachtenberg L, et al: The cerebral cortex overlying periventricular leukomalacia: analysis of pyramidal neurons. Brain Pathol. 20:803–814. 2010. View Article : Google Scholar : PubMed/NCBI
3	Barkovich J, Millen J and Dobyns B: A developmental and genetic classification for midbrain-hindbrain malformations. Brain. 132:3199–3230. 2009. View Article : Google Scholar : PubMed/NCBI
4	Lo Nigro C, Chong CS, Smith AC, Dobyns WB, Carrozzo R and Ledbetter DH: Point mutations and an intragenic deletion in LIS1, the lissencephaly causative gene in isolated lissencephaly sequence and Miller-Dieker syndrome. Hum Mol Genet. 6:157–164. 1997.PubMed/NCBI
5	Tsai JW, Bremner KH and Vallee RB: Dual subcellular roles for LIS1 and dynein in radial neuronal migration in live brain tissue. Nat Neurosci. 10:970–979. 2007. View Article : Google Scholar
6	Yamada M, Toba S, Yoshida Y, et al: LIS1 and NDEL1 coordinate the plus-end-directed transport of cytoplasmic dynein. EMBO J. 27:2471–2483. 2008. View Article : Google Scholar : PubMed/NCBI
7	Bi W, Sapir T, Shchelochkov OA, et al: Increased LIS1 expression affects human and mouse brain development. Nat Genet. 41:168–177. 2009. View Article : Google Scholar : PubMed/NCBI
8	Haverfield V, Whited J, Petras S, Dobyns B and Das S: Intragenic deletions and duplications of the LIS1 and DCX genes: a major disease-causing mechanism in lissencephaly and subcortical band heterotopia. Eur J Hum Genet. 17:911–918. 2008. View Article : Google Scholar : PubMed/NCBI
9	Wynshaw-Boris A: Lissencephaly and LIS1: insights into the molecular mechanisms of neuronal migration and development. Clin Genet. 72:296–304. 2007. View Article : Google Scholar : PubMed/NCBI
10	Carthew W: Gene regulation by microRNAs. Curr Opin Genet Dev. 16:203–208. 2006. View Article : Google Scholar
11	Bushati N and Cohen M: microRNA functions. Annu Rev Cell Dev Biol. 23:175–205. 2007. View Article : Google Scholar
12	Sayed D and Abdellatif M: MicroRNAs in development and disease. Physiol Rev. 91:827–887. 2011. View Article : Google Scholar : PubMed/NCBI
13	Qureshi IA and Mehler MF: Emerging roles of non-coding RNAs in brain evolution, development, plasticity and disease. Nat Rev Neurosci. 13:528–541. 2012. View Article : Google Scholar : PubMed/NCBI
14	Castoldi M, Schmidt S, Benes V, et al: A sensitive array for microRNA expression profiling (miChip) based on locked nucleic acids (LNA). RNA. 12:913–929. 2006. View Article : Google Scholar : PubMed/NCBI
15	Meng F, Henson R, Wehbe-Janek H, et al: MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology. 133:647–658. 2007. View Article : Google Scholar : PubMed/NCBI
16	Wang J and Ruan K: miR-200c affects the mRNA expression of E-cadherin by regulating the mRNA level of TCF8 during post-natal epididymal development in juvenile rats. Acta Biochim Biophys Sin (Shanghai). 42:628–634. 2010. View Article : Google Scholar : PubMed/NCBI
17	Nakanishi N, Nakagawa Y, Tokushige N, et al: The up-regulation of microRNA-335 is associated with lipid metabolism in liver and white adipose tissue of genetically obese mice. Biochem Biophys Res Commun. 385:492–496. 2009. View Article : Google Scholar : PubMed/NCBI
18	Wu AJ, Hua H, Munson SH and McDevitt HO: Tumor necrosis factor-alpha regulation of CD4⁺CD25⁺T cell levels in NOD mice. Proc Natl Acad Sci USA. 99:12287–12292. 2002. View Article : Google Scholar : PubMed/NCBI
19	Shenouda SK and Alahari SK: MicroRNA function in cancer: oncogene or a tumor suppressor? Cancer Metastasis Rev. 28:369–378. 2009. View Article : Google Scholar : PubMed/NCBI
20	Norman L and Sarnow P: Modulation of hepatitis C virus RNA abundance and the isoprenoid biosynthesis pathway by microRNA miR-122 involves distinct mechanisms. J Virol. 84:666–670. 2010. View Article : Google Scholar : PubMed/NCBI
21	Hui AB, Lenarduzzi M, Krushel T, et al: Comprehensive MicroRNA profiling for head and neck squamous cell carcinomas. Clin Cancer Res. 16:1129–1139. 2010. View Article : Google Scholar : PubMed/NCBI
22	Wong M, Yam P, Ching P, et al: Rho GTPase-activating protein deleted in liver cancer suppresses cell proliferation and invasion in hepatocellular carcinoma. Cancer Res. 65:8861–8868. 2005. View Article : Google Scholar : PubMed/NCBI
23	Gitlin L, Karelsky S and Andino R: Short interfering RNA confers intracellular antiviral immunity in human cells. Nature. 418:430–434. 2002. View Article : Google Scholar : PubMed/NCBI
24	Takase I, Shigeto H, Suzuki SO, Kikuchi H, Ohyagi Y and Kira J: Prenatal freeze lesioning produces epileptogenic focal cortical dysplasia. Epilepsia. 49:997–1010. 2008. View Article : Google Scholar : PubMed/NCBI
25	Calin GA, Sevignani C, Dumitru CD, et al: Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci USA. 101:2999–3004. 2004. View Article : Google Scholar : PubMed/NCBI
26	Yingling J1, Youn YH, Darling D, et al: Neuroepithelial stem cell proliferation requires LIS1 for precise spindle orientation and symmetric division. Cell. 132:474–486. 2008. View Article : Google Scholar : PubMed/NCBI
27	Wegiel J, Kuchna I, Nowicki K, et al: The neuropathology of autism: defects of neurogenesis and neuronal migration, and dysplastic changes. Acta Neuropathol. 119:755–770. 2010. View Article : Google Scholar : PubMed/NCBI
28	Manent JB, Wang Y, Chang Y, Paramasivam M and LoTurco JJ: Dcx reexpression reduces subcortical band heterotopia and seizure threshold in an animal model of neuronal migration disorder. Nat Med. 15:84–90. 2009. View Article : Google Scholar
29	Manzini MC and Walsh CA: What disorders of cortical development tell us about the cortex: one plus one does not always make two. Curr Opin Genet Dev. 21:333–339. 2011. View Article : Google Scholar : PubMed/NCBI
30	Guerrini R and Parrini E: Neuronal migration disorders. Neurobiol Dis. 38:154–166. 2010. View Article : Google Scholar
31	Walser M, Hansén A, Svensson A, et al: Peripheral administration of bovine GH regulates the expression of cerebrocortical beta-globin, GABAB receptor 1, and the Lissencephaly-1 protein (LIS-1) in adult hypophysectomized rats. Growth Horm IGF Res. 21:16–24. 2011. View Article : Google Scholar : PubMed/NCBI
32	Cappello S, Monzo P and Vallee RB: NudC is required for interkinetic nuclear migration and neuronal migration during neocortical development. Dev Biol. 357:326–335. 2011. View Article : Google Scholar : PubMed/NCBI
33	Schepeler T, Reinert JT, Ostenfeld MS, et al: Diagnostic and prognostic microRNAs in stage II colon cancer. Cancer Res. 68:6416–6424. 2008. View Article : Google Scholar : PubMed/NCBI
34	Zhang C: Novel functions for small RNA molecules. Curr Opin Mol Ther. 11:641–651. 2009.PubMed/NCBI
35	Winter J, Jung S, Keller S, Gregory RI and Diederichs S: Many roads to maturity: microRNA biogenesis pathways and their regulation. Nat Cell Biol. 11:228–234. 2009. View Article : Google Scholar : PubMed/NCBI
36	Goswami S, Angkasekwinai P, Shan M, et al: Divergent functions for airway epithelial matrix metalloproteinase 7 and retinoic acid in experimental asthma. Nat Immunol. 10:496–503. 2009. View Article : Google Scholar : PubMed/NCBI
37	Davalos V and Esteller M: MicroRNAs and cancer epigenetics: a macrorevolution. Curr Opin Oncol. 22:35–45. 2010. View Article : Google Scholar
38	Verrotti A, Spalice A, Ursitti F, et al: New trends in neuronal migration disorders. Eur J Paediatr Neurol. 14:1–12. 2010. View Article : Google Scholar
39	Huang YJ, Zheng G, Lu XP, Lu HY and Mo XM: Proteomics of epilepsy induced by focal disorder of cortical development. Chin J Neuromed. 9:670–673. 2010.
40	Sand M, Sand D, Altmeyer P and Bechara FG: MicroRNA in non-melanoma skin cancer. Cancer Biomark. 11:253–257. 2012.PubMed/NCBI
41	Hippenmeyer S, Youn YH, Moon HM, et al: Genetic mosaic dissection of Lis1 and Ndel1 in neuronal migration. Neuron. 68:695–709. 2010. View Article : Google Scholar : PubMed/NCBI
42	Saugstad JA: MicroRNAs as effectors of brain function with roles in ischemia and injury, neuroprotection, and neurodegeneration. J Cereb Blood Flow Metab. 30:1564–1576. 2010. View Article : Google Scholar : PubMed/NCBI
43	Shen K, Liang Q, Xu K, et al: MiR-139 inhibits invasion and metastasis of colorectal cancer by targeting the type I insulin-like growth factor receptor. Biochem Pharmacol. 84:320–330. 2012. View Article : Google Scholar : PubMed/NCBI