miR 181a [Neurosurgery Wiki]

This page is read only. You can view the source, but not change it. Ask your administrator if you think this is wrong.
====== miR 181a ======

Shi et al., showed that hsa-miR-181a and hsa-miR-181b functioned as [[tumor suppressor]]s which triggered growth [[inhibition]], induced [[apoptosis]] and inhibited invasion in [[glioma]] cells. Furthermore, the tumor-suppressive effect of hsa-miR-181b in glioma cells was more apparent than the effect of hsa-miR-181a. These findings suggest aberrantly down-regulated hsa-miR-181a and hsa-miR-181b may be critical factors that contribute to malignant appearance in human gliomas
((Shi L, Cheng Z, Zhang J, Li R, Zhao P, Fu Z, You Y. hsa-mir-181a and
hsa-mir-181b function as tumor suppressors in human glioma cells. Brain Res. 2008
Oct 21;1236:185-93. doi: 10.1016/j.brainres.2008.07.085. Epub 2008 Jul 30. PubMed
PMID: 18710654.
)).

ATP2B2 target gene could be regulated by has-mir-181a to involve in calcium signaling pathway
((Yu J, Cai X, He J, Zhao W, Wang Q, Liu B. Microarray-based analysis of gene
regulation by transcription factors and microRNAs in glioma. Neurol Sci. 2013
Aug;34(8):1283-9. doi: 10.1007/s10072-012-1228-1. Epub 2012 Dec 5. PubMed PMID:
23212403.
)).

Ma et al., identified microRNA-181a (miR-181a) as a critical MicroRNA in opening BTB. MicroRNA-181a expression was upregulated in glioma endothelial cells (GECs), which were obtained by coculturing endothelial cells (ECs) with glioma cells. Overexpression of miR-181a resulted in an impaired and permeability increased BTB, and meanwhile reduced the expression of zonula occluden (ZO)-1, occludin, and claudin-5. Kruppel-like factor 6 (KLF6), a transcription factor of the zinc-finger family, was downregulated in GECs. Mechanistic investigations defined it as a direct and functional downstream target of miR-181a, which was involved in the regulation of BTB permeability and the expression of ZO-1, occludin, and claudin-5. Furthermore, luciferase assays and chromatin immunoprecipitation assays showed that KLF6 upregulated the promoter activities and interacted with the promoters of ZO-1, occludin, and claudin-5 in GECs. Collectively, we showed the possibility that overexpression of miR-181a contributes to the increased permeability of BTB by targeting KLF6, thereby revealing potential therapeutic targets for the treatment of brain gliomas
((Ma J, Yao Y, Wang P, Liu Y, Zhao L, Li Z, Li Z, Xue Y. MiR-181a regulates
blood-tumor barrier permeability by targeting Krüppel-like factor 6. J Cereb
Blood Flow Metab. 2014 Nov;34(11):1826-36. doi: 10.1038/jcbfm.2014.152. Epub 2014
Sep 3. PubMed PMID: 25182666; PubMed Central PMCID: PMC4269760.
)).

Wu et al., identified miR 181a, which may have a biological function, particularly during the early stages after nerve allotransplantation under FK506 immunosuppression
((Wu SC, Rau CS, Yang JC, Lu TH, Wu YC, Chen YC, Tzeng SL, Wu CJ, Lin CW, Hsieh 
CH. Identification of Circulating MicroRNAs in a Mouse Model of Nerve Allograft
Transplantation under FK506 Immunosuppression by Illumina Small RNA Deep
Sequencing. Dis Markers. 2015;2015:863192. doi: 10.1155/2015/863192. Epub 2015
Sep 8. PubMed PMID: 26435568; PubMed Central PMCID: PMC4578739.
)).

In HMOX1-transfected astrocytes, rno-miR-140*, rno-miR-17, and rno-miR-16 were significantly up-regulated, and rno-miR-297, rno-miR-206, rno-miR-187, rno-miR-181a, rno-miR-138 and rno-miR-29c were down-regulated, compared to sham-transfected controls
((Lin SH, Song W, Cressatti M, Zukor H, Wang E, Schipper HM. Heme oxygenase-1
modulates microRNA expression in cultured astroglia: implications for chronic
brain disorders. Glia. 2015 Jul;63(7):1270-84. doi: 10.1002/glia.22823. Epub 2015
Mar 25. PubMed PMID: 25820186.
)).

Sharma et al., measured six downstream MicroRNA targets of EZH2 and found significant downregulation of four (miR-181a/b and 200b/c) in GBM
((Sharma V, Purkait S, Takkar S, Malgulwar PB, Kumar A, Pathak P, Suri V, Sharma
MC, Suri A, Kale SS, Kulshreshtha R, Sarkar C. Analysis of EZH2: micro-RNA
network in low and high grade astrocytic tumors. Brain Tumor Pathol. 2016
Apr;33(2):117-28. doi: 10.1007/s10014-015-0245-1. Epub 2016 Jan 8. PubMed PMID:
26746204.
)).

Huang et al., showed that miR-181a and it targets ANGPT2 and LAMC1 might be predictors of prognosis in GBM patients
((Huang SX, Zhao ZY, Weng GH, He XY, Wu CJ, Fu CY, Sui ZY, Zhong XM, Liu T. The 
correlation of microRNA-181a and target genes with poor prognosis of glioblastoma
patients. Int J Oncol. 2016 Jul;49(1):217-24. doi: 10.3892/ijo.2016.3511. Epub
2016 May 9. PubMed PMID: 27176932.
)).

CASC2 could inhibit the miR-181a expression by direct targeting in TMZ-resistant glioma cells. CASC2 up-regulated PTEN protein and down-regulated p-AKT protein through regulating miR-181a, and the effect of CASC2 on PTEN and p-AKT could be partially restored by miR-181a. With TMZ-resistant glioma tissues, miR-181a was up-regulated while PTEN was down-regulated. Taken together, these observations suggest CASC2 up-regulates PTEN through direct inhibiting miR-181a and plays an important role in glioma sensitivity to TMZ and may serve as a potential target for cancer diagnosis and treatment
((Liao Y, Shen L, Zhao H, Liu Q, Fu J, Guo Y, Peng R, Cheng L. LncRNA CASC2
Interacts With miR-181a to Modulate Glioma Growth and Resistance to TMZ Through
PTEN Pathway. J Cell Biochem. 2017 Jul;118(7):1889-1899. doi: 10.1002/jcb.25910. 
Epub 2017 Feb 13. PubMed PMID: 28121023.
)).

High Notch2 expression together with low miR-181a expression was correlated with a shorter median overall survival for GBM patients. Together, these data show that miR-181a may play an essential role in GSC formation and GBM progression by targeting Notch2, suggesting that Notch2 and miR-181a have potential prognostic value as tumor biomarkers in GBM patients
((Huang SX, Zhao ZY, Weng GH, He XY, Wu CJ, Fu CY, Sui ZY, Ma YS, Liu T.
Upregulation of miR-181a suppresses the formation of glioblastoma stem cells by
targeting the Notch2 oncogene and correlates with good prognosis in patients with
glioblastoma multiforme. Biochem Biophys Res Commun. 2017 May
13;486(4):1129-1136. doi: 10.1016/j.bbrc.2017.04.008. Epub 2017 Apr 4. PubMed
PMID: 28389242.
)).

A transient increase in miR-181a expression was observed after conditioned fear conditioning (CFC) and object location task (OLT) training. Selective overexpression or inhibition of miR-181a in the dorsal hippocampus (DH) via the injection of a miR-181a agomir or antagomir enhanced or impaired the CFC- and OLT-dependent memory formation, respectively. Using bioinformatics and luciferase assays, we identified PRKAA1 as a potential target gene of miR-181a. After CFC or OLT training, the expression and activity of PRKAA1 decreased as miR-181a expression increased and was effectively blocked by the miR-181a antagomir. Moreover, microinjection of the PRKAA1 agonist AICAR or inhibitor compound C in the DH reversed the roles of the miR-181a agomir or antagomir in CFC- and OLT-dependent memory formation. In conclusion, this work provides novel evidence describing the role and mechanism of miR-181a in hippocampus-dependent memory formation, which sheds light on the potential regulation of cognition and future treatments for cognitive disorders
((Zhang SF, Chen JC, Zhang J, Xu JG. miR-181a involves in the
hippocampus-dependent memory formation via targeting PRKAA1. Sci Rep. 2017 Aug
16;7(1):8480. doi: 10.1038/s41598-017-09095-3. PubMed PMID: 28814760; PubMed
Central PMCID: PMC5559581.
)).


[[miR 181a]] plays critical roles in multiple [[cancer]]s; however, its precise mechanisms in [[glioma]] have not been well clarified. The goal of a study of Wang et al., from  the Harbin Medical University, [[Harbin]], [[China]], was to evaluate the interaction between [[Kaiso]] and miR-181a in [[glioma]].

[[Quantitative real-time]] [[PCR]] (qRT-PCR) was performed to detect the levels of Kaiso and miR-181a in glioma [[tissue]]s and [[cell line]]s. [[Cell proliferation]], [[invasion]], and the [[Epithelial-mesenchymal-transition]] (EMT) were evaluated to analyze the biological functions of miR-181a and Kaiso in glioma cells. The [[mRNA]] and [[protein]] levels of Kaiso were measured by qRT-PCR and [[western blot]]ting, respectively. Meanwhile, [[luciferase]] assays were performed to validate Kaiso as a miR-181a target in glioma cells.

They found that the level of miR-181a was the lowest among miR-181a-d in glioma tissues and cell lines, and the low level of miR-181a was closely associated with the increased expression of Kaiso in glioma tissues. Moreover, [[transfection]] of miR-181a significantly inhibited the [[proliferation]], invasion, and EMT of glioma cells, whereas [[knockdown]] of miR-181a had the opposite effect. [[Bioinformatics]] analysis predicted that Kaiso was a potential target gene of miR-181a, and the luciferase reporter assay demonstrated that miR-181a could directly target Kaiso. In addition, Kaiso silencing had similar effects as miR-181a [[overexpression]] in glioma cells, whereas overexpression of Kaiso in glioma cells partially reversed the inhibitory effects of the miR-181a mimic. 

miR-181a inhibited the proliferation, invasion, and EMT of glioma cells by directly targeting and downregulating Kaiso expression
((Wang L, Ma J, Wang X, Peng F, Chen X, Zheng B, Wang C, Dai Z, Ai J, Zhao S.
Kaiso (ZBTB33) Downregulation by MicroRNA-181a Inhibits Cell Proliferation,
Invasion, and the Epithelial-Mesenchymal Transition in Glioma Cells. Cell Physiol
Biochem. 2018 Jul 23;48(3):947-958. doi: 10.1159/000491963. [Epub ahead of print]
PubMed PMID: 30036882.
)).