MicroRNA‑29a inhibits mesenchymal stem cell viability and proliferation by targeting Roundabout 1

Zhang,Yudong; Zhou,Shenghua

doi:10.3892/mmr.2015.4183

MicroRNA‑29a inhibits mesenchymal stem cell viability and proliferation by targeting Roundabout 1

Authors:
- Yudong Zhang
- Shenghua Zhou
View Affiliations

Affiliations: Department of Cardiology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China
Published online on: August 5, 2015 https://doi.org/10.3892/mmr.2015.4183
Pages: 6178-6184

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Secreted Slit glycoproteins and their Roundabout (Robo) receptors have been identified as important axon guidance molecules. The pivotal role of Slit‑Robo signaling is in regulating cell proliferation. MicroRNAs (miRNAs), a class of small non‑coding RNAs, function as critical regulators of gene expression by binding to the 3'‑untranslated region of mRNAs and causing mRNA degradation or translational repression. The present study demonstrated that downregulation of Robo1 using small interfering RNA inhibited mesenchymal stem cell (MSC) proliferation. Additionally, four miRNAs (miR), including miR‑218, miR‑29a, miR‑146 and miR‑148, inhibited the protein expression of Robo1 in the MSCs, with miR‑29 having the most marked effect. A luciferase reporter assay identified Robo1 as a novel target of miR‑29a. Overexpression of miR‑29a suppressed the protein expression levels of Robo1 and Slit2 and inhibited the viability and proliferation of the MSCs. By contrast, overexpression of Robo1 partly rescued these inhibitory effects of miR‑29a on the MSCs confirming that miR‑29a inhibited MSC viability and proliferation, at least partially, by directly targeting Robo1. These results indicated that the miR‑29a/Robo1 axis is crucial for the regulation of MSC viability and proliferation, suggesting that miR‑29a may serve as a potential clinical target for MSC expansion and stem cell transplantation.

View Figures

View References

1	Bayraktar UD and Ciurea SO: Strategies in haploidentical stem cell transplantation in adults. Turk J Haematol. 30:342–350. 2013. View Article : Google Scholar
2	Tanabe S: Role of mesenchymal stem cells in cell life and their signaling. World J Stem Cells. 6:24–32. 2014. View Article : Google Scholar : PubMed/NCBI
3	Das M, Sundell IB and Koka PS: Adult mesenchymal stem cells and their potency in the cell-based therapy. J Stem Cells. 8:1–16. 2013.
4	Moss EG: MicroRNAs: Hidden in the genome. Curr Biol. 12:R138–140. 2002. View Article : Google Scholar : PubMed/NCBI
5	Sarkar D, Leung EY, Baguley BC, Finlay GJ and Askarian-Amiri ME: Epigenetic regulation in human melanoma: Past and future. Epigenetics. Jan 14–2015.Epub ahead of print. View Article : Google Scholar : PubMed/NCBI
6	Peterson SM, Thompson JA, Ufkin ML, Sathyanarayana P, Liaw L and Congdon CB: Common features of microRNA target prediction tools. Front Genet. 5:232014. View Article : Google Scholar : PubMed/NCBI
7	Lewis BP, Burge CB and Bartel DP: Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 120:15–20. 2005. View Article : Google Scholar : PubMed/NCBI
8	Krek A, Grun D, Poy MN, et al: Combinatorial microRNA target predictions. Nat Genet. 37:495–500. 2005. View Article : Google Scholar : PubMed/NCBI
9	Andrews W, Barber M, Hernadez-Miranda LR, et al: The role of Slit-Robo signaling in the generation, migration and morphological differentiation of cortical interneurons. Dev Biol. 313:648–658. 2008. View Article : Google Scholar
10	Yuen DA and Robinson LA: Slit2-Robo signaling: A novel regulator of vascular injury. Curr Opin Nephrol Hypertens. 22:445–451. 2013. View Article : Google Scholar : PubMed/NCBI
11	Wang G, Li Y, Wang XY, et al: Slit/Robo1 signaling regulates neural tube development by balancing neuroepithelial cell proliferation and differentiation. Exp Cell Res. 319:1083–1093. 2013. View Article : Google Scholar : PubMed/NCBI
12	Dontula R, Dinasarapu A, Chetty C, et al: MicroRNA 203 modulates glioma cell migration via Robo1/ERK/MMP-9 signaling. Genes Cancer. 4:285–296. 2013. View Article : Google Scholar : PubMed/NCBI
13	Huang L, Xu Y, Yu W, et al: Effect of Robo1 on retinal pigment epithelial cells and experimental proliferative vitreoretinopathy. Invest Ophthalmol Vis Sci. 51:3193–3204. 2010. View Article : Google Scholar : PubMed/NCBI
14	Je EM, Gwak M, Oh H, et al: Frameshift mutations of axon guidance genes ROBO1 and ROBO2 in gastric and colorectal cancers with microsatellite instability. Pathology. 45:645–650. 2013. View Article : Google Scholar : PubMed/NCBI
15	Sun H, Dai K, Tang T and Zhang X: Regulation of osteoblast differentiation by slit2 in osteoblastic cells. Cells Tissues Organs. 190:69–80. 2009. View Article : Google Scholar
16	Smith-Berdan sec, Schepers K, Ly A, Passegue E and Forsberg EC: Dynamic expression of the Robo ligand Slit2 in bone marrow cell populations. Cell Cycle. 11:675–682. 2012. View Article : Google Scholar : PubMed/NCBI
17	Kim KS, Kim JS, Lee MR, Jeong HS and Kim J: A study of microRNAs in silico and in vivo: Emerging regulators of embryonic stem cells. FEBS J. 276:2140–2149. 2009. View Article : Google Scholar : PubMed/NCBI
18	Fish JE, Wythe JD, Xiao T, et al: A Slit/miR-218/Robo regulatory loop is required during heart tube formation in zebrafish. Development. 138:1409–1419. 2011. View Article : Google Scholar : PubMed/NCBI
19	Choi E and Hwang KC: MicroRNAs as novel regulators of stem cell fate. World J Stem Cells. 5:172–187. 2013. View Article : Google Scholar : PubMed/NCBI
20	Guerit D, Brondello JM, Chuchana P, et al: FoxO3A regulation by miRNA-29a controls chondrogenic differentiation of mesenchymal stem cells and cartilage formation. Stem Cells Dev. 23:1195–1205. 2014. View Article : Google Scholar : PubMed/NCBI
21	Lin X, Wu L, Zhang Z, et al: MiR-335-5p promotes chondrogenesis in mouse mesenchymal stem cells and is regulated through two positive feedback loops. J Bone Miner Res. 29:1575–1585. 2013. View Article : Google Scholar : PubMed/NCBI
22	Yan C, Wang Y, Shen XY, et al: MicroRNA regulation ass°Ciated chondrogenesis of mouse MSCs grown on polyhydroxyalkanoates. Biomaterials. 32:6435–6444. 2011. View Article : Google Scholar : PubMed/NCBI
23	Chen S, Yang L, Jie Q, et al: MicroRNA125b suppresses the proliferation and osteogenic differentiation of human bone marrowderived mesenchymal stem cells. Mol Med Rep. 9:1820–1826. 2014.PubMed/NCBI
24	Mao J, Lv Z and Zhuang Y: MicroRNA-23a is involved in tumor necrosis factor-alpha induced apoptosis in mesenchymal stem cells and myocardial infarction. Exp Mol Pathol. 2013.