MicroRNA‑138‑5p regulates neural stem cell proliferation and differentiation in vitro by targeting TRIP6 expression

Wang,Juan; Li,Jixia; Yang,Jian; Zhang,Lianguo; Gao,Shane; Jiao,Fei; Yi,Maoli; Xu,Jun

doi:10.3892/mmr.2017.7504

MicroRNA‑138‑5p regulates neural stem cell proliferation and differentiation in vitro by targeting TRIP6 expression

Authors:
- Juan Wang
- Jixia Li
- Jian Yang
- Lianguo Zhang
- Shane Gao
- Fei Jiao
- Maoli Yi
- Jun Xu
View Affiliations

Affiliations: Stem Cell Center, East Hospital, Tongji University School of Medicine, Shanghai 200120, P.R. China, Clinical Laboratory, Yantaishan Hospital, Yantai, Shandong 264000, P.R. China, Administration Office, Yantai Blood Station, Yantai, Shandong 264000, P.R. China, Department of Thoracic Surgery, Affiliated Hospital of Binzhou Medical College, Binzhou, Shandong 256603, P.R. China, Department of Biotechnology and Molecular, Binzhou Medical College, Yantai, Shandong 264003, P.R. China, Laboratory of Yantai Yuhuangding Hospital, Yantai, Shandong 264003, P.R. China
Published online on: September 18, 2017 https://doi.org/10.3892/mmr.2017.7504
Pages: 7261-7266
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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

Research on neural stem cells (NSCs) has recently focused on microRNAs (miRNAs), a class of small non‑coding RNAs that have crucial roles in regulating NSC proliferation and differentiation. In the present study, a quantitative‑polymerase chain reaction assay revealed that the expression of miRNA (miR)‑138‑5p was significantly decreased during neural differentiation of NSCs in vitro. Overexpression of miR‑138‑5p reduced NSC proliferation and increased NSC differentiation. Furthermore, suppression of miR‑138‑5p via transfection with a miRNA inhibitor enhanced NSC proliferation and attenuated NSC differentiation. Additionally, expression of thyroid hormone receptor interacting protein 6 (TRIP6), a critical regulator of NSCs, was negatively correlated with the miR‑138‑5p level. A luciferase assay demonstrated that miR‑138‑5p regulate TRIP6 by directly binding the 3'‑untranslated region of the mRNA. Additionally, upregulation of TRIP6 rescued the NSC proliferation deficiency induced by miR‑138‑5p and abolished miR‑138‑5p‑promoted NSCs differentiation. By contrast, downregulation of TRIP6 produced the opposite effect on proliferation and differentiation of NSCs transfected with anti‑miR‑138‑5p. Taken together, the data suggest that miR‑138‑5p regulates NSCs proliferation and differentiation, and may be useful in developing novel treatments for neurological disorders via manipulation of miR‑138‑5p in NSCs.

View Figures

View References

1	Liu S, Yin F, Zhang J, Wicha MS, Chang AE, Fan W, Chen L, Fan M and Li Q: Regulatory roles of miRNA in the human neural stem cell transformation to glioma stem cells. J Cell Biochem. 115:1368–1380. 2014. View Article : Google Scholar : PubMed/NCBI
2	Chaker Z, Codega P and Doetsch F: A mosaic world: Puzzles revealed by adult neural stem cell heterogeneity. Wiley Interdiscip Rev Dev Biol. 5:640–658. 2016. View Article : Google Scholar : PubMed/NCBI
3	Chung SY, Kishinevsky S, Mazzulli JR, Graziotto J, Mrejeru A, Mosharov EV, Puspita L, Valiulahi P, Sulzer D, Milner TA, et al: Parkin and PINK1 patient iPSC-derived midbrain dopamine neurons exhibit mitochondrial dysfunction and α-synuclein accumulation. Stem Cell Reports. 7:664–677. 2016. View Article : Google Scholar : PubMed/NCBI
4	Cheng A, Hou Y and Mattson MP: Mitochondria and neuroplasticity. ASN Neuro. 2:e000452010. View Article : Google Scholar : PubMed/NCBI
5	Rao P, Benito E and Fischer A: MicroRNAs as biomarkers for CNS disease. Front Mol Neurosci. 6:392013. View Article : Google Scholar : PubMed/NCBI
6	Shi X, Yan C, Liu B, Yang C, Nie X, Wang X, Zheng J, Wang Y and Zhu Y: miR-381 regulates neural stem cell proliferation and differentiation via regulating Hes1 expression. PLoS One. 10:e01389732015. View Article : Google Scholar : PubMed/NCBI
7	Ryu JR, Hong CJ, Kim JY, Kim EK, Sun W and Yu SW: Control of adult neurogenesis by programmed cell death in the mammalian brain. Mol Brain. 9:432016. View Article : Google Scholar : PubMed/NCBI
8	Shukla GC, Singh J and Barik S: MicroRNAs: Processing, maturation, target recognition and regulatory functions. Mol Cell Pharmacol. 3:83–92. 2011.PubMed/NCBI
9	Bartel DP: MicroRNAs: Target recognition and regulatory functions. Cell. 136:215–233. 2009. View Article : Google Scholar : PubMed/NCBI
10	Meza-Sosa KF, Pedraza-Alva G and Pérez-Martínez L: microRNAs: Key triggers of neuronal cell fate. Front Cell Neurosci. 8:1752014. View Article : Google Scholar : PubMed/NCBI
11	Palmer TD, Markakis EA, Willhoite AR, Safar F and Gage FH: Fibroblast growth factor-2 activates a latent neurogenic program in neural stem cells from diverse regions of the adult CNS. J Neurosci. 19:8487–8497. 1999.PubMed/NCBI
12	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
13	Lai YJ, Li MY, Yang CY, Huang KH, Tsai JC and Wang TW: TRIP6 regulates neural stem cell maintenance in the postnatal mammalian subventricular zone. Dev Dyn. 243:1130–1142. 2014. View Article : Google Scholar : PubMed/NCBI
14	Lv K, Chen L, Li Y, Li Z, Zheng P, Liu Y, Chen J and Teng J: Trip6 promotes dendritic morphogenesis through dephosphorylated GRIP1-dependent myosin VI and F-actin organization. J Neurosci. 35:2559–2571. 2015. View Article : Google Scholar : PubMed/NCBI
15	Huang Y, Liu X and Wang Y: MicroRNA-378 regulates neural stem cell proliferation and differentiation in vitro by modulating Tailless expression. Biochem Biophys Res Commun. 466:214–220. 2015. View Article : Google Scholar : PubMed/NCBI
16	Tandon PN and Seth P: Cell therapy for neurological disorders: The elusive goal. Neurol India. 64:612–623. 2016. View Article : Google Scholar : PubMed/NCBI
17	Xiao L, Zhou H, Li XP, Chen J, Fang C, Mao CX, Cui JJ, Zhang W, Zhou HH, Yin JY and Liu ZQ: MicroRNA-138 acts as a tumor suppressor in non small cell lung cancer via targeting YAP1. Oncotarget. 7:40038–40046. 2016. View Article : Google Scholar : PubMed/NCBI
18	Liu Y, Zhang W, Liu K, Liu S, Ji B and Wang Y: miR-138 suppresses cell proliferation and invasion by inhibiting SOX9 in hepatocellular carcinoma. Am J Transl Res. 8:2159–2168. 2016.PubMed/NCBI
19	Xu C, Fu H, Gao L, Wang L, Wang W, Li J, Li Y, Dou L, Gao X, Luo X, et al: BCR-ABL/GATA1/miR-138 mini circuitry contributes to the leukemogenesis of chronic myeloid leukemia. Oncogene. 33:44–54. 2014. View Article : Google Scholar : PubMed/NCBI
20	Tian S, Guo X, Yu C, Sun C and Jiang J: miR-138-5p suppresses autophagy in pancreatic cancer by targeting SIRT1. Oncotarget. 8:11071–11082. 2017.PubMed/NCBI
21	Yu C, Wang M, Li Z, Xiao J, Peng F, Guo X, Deng Y, Jiang J and Sun C: MicroRNA-138-5p regulates pancreatic cancer cell growth through targeting FOXC1. Cell Oncol (Dordr). 38:173–181. 2015. View Article : Google Scholar : PubMed/NCBI
22	Schroder J, Ansaloni S, Schilling M, Liu T, Radke J, Jaedicke M, Schjeide BM, Mashychev A, Tegeler C, Radbruch H, et al: MicroRNA-138 is a potential regulator of memory performance in humans. Front Hum Neurosci. 8:5012014.PubMed/NCBI
23	Castaneda P, Muñoz M, Garcia-Rojo G, Ulloa JL, Bravo JA, Márquez R, García-Pérez MA, Arancibia D, Araneda K, Rojas PS, et al: Association of N-cadherin levels and downstream effectors of Rho GTPases with dendritic spine loss induced by chronic stress in rat hippocampal neurons. J Neurosci Res. 93:1476–1491. 2015. View Article : Google Scholar : PubMed/NCBI
24	Wang X, Tan L, Lu Y, Peng J, Zhu Y, Zhang Y and Sun Z: MicroRNA-138 promotes tau phosphorylation by targeting retinoic acid receptor alpha. FEBS Lett. 589:726–729. 2015. View Article : Google Scholar : PubMed/NCBI
25	Lin VT and Lin FT: TRIP6: An adaptor protein that regulates cell motility, antiapoptotic signaling and transcriptional activity. Cell Signal. 23:1691–1697. 2011. View Article : Google Scholar : PubMed/NCBI
26	Willier S, Butt E, Richter GH, Burdach S and Grunewald TG: Defining the role of TRIP6 in cell physiology and cancer. Biol Cell. 103:573–591. 2011. View Article : Google Scholar : PubMed/NCBI
27	Grunewald TG, Willier S, Janik D, Unland R, Reiss C, da Costa Prazeres O, Buch T, Dirksen U, Richter GH, Neff F, et al: The Zyxin-related protein thyroid receptor interacting protein 6 (TRIP6) is overexpressed in Ewing's sarcoma and promotes migration, invasion and cell growth. Biol Cell. 105:535–547. 2013. View Article : Google Scholar : PubMed/NCBI
28	Hoffman LM, Nix DA, Benson B, Boot-Hanford R, Gustafsson E, Jamora C, Menzies AS, Goh KL, Jensen CC, Gertler FB, et al: Targeted disruption of the murine zyxin gene. Mol Cell Biol. 23:70–79. 2003. View Article : Google Scholar : PubMed/NCBI