Differential effects of miR‑34c‑3p and miR‑34c‑5p on the proliferation, apoptosis and invasion of glioma cells

Wu,Zhendong; Wu,Yupeng; Tian,Ye; Sun,Xiaofeng; Liu,Jixiang; Ren,Hongbo; Liang,Chaohui; Song,Ligang; Hu,Hongchao; Wang,Liqun; Jiao,Baohua

doi:10.3892/ol.2013.1579

November 2013 Volume 6 Issue 5

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November 2013 Volume 6 Issue 5

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Article

Differential effects of miR‑34c‑3p and miR‑34c‑5p on the proliferation, apoptosis and invasion of glioma cells

Authors:
- Zhendong Wu
- Yupeng Wu
- Ye Tian
- Xiaofeng Sun
- Jixiang Liu
- Hongbo Ren
- Chaohui Liang
- Ligang Song
- Hongchao Hu
- Liqun Wang
- Baohua Jiao
View Affiliations / Copyright

Affiliations: Department of Neurosurgery, The Second Hospital of Hebei Medical University, Shi Jiazhuang, Hebei 050000, P.R. China, Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China, Department of Neurosurgery, Handan Central Hospital, Handan, Hebei 056000, P.R. China
Pages: 1447-1452
|
Published online on: September 12, 2013

https://doi.org/10.3892/ol.2013.1579
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Abstract

Glioblastoma is the most malignant and common intrinsic brain tumor, but the molecular mechanism of glioma pathophysiology is poorly understood. Recent data have shown that microRNAs regulate the expression of several genes associated with human cancer. In the present study, the function of miR‑34c in glioma cells was analyzed. It was demonstrated that miR‑34c‑3p and miR‑34c‑5p were downregulated in gliomas, by performing qPCR on tumor tissues from glioma patients and glioma cell lines, compared with normal brain tissues and a normal glial cell line. Furthermore, the miR‑34c expression was found to be inversely correlated with glioma WHO grades. Overexpression of miR‑34c‑3p inhibited U251 and U87 cell proliferation; however, miR‑34c‑5p only had an effect on U251 cells. Transfection with miR‑34c‑3p or miR‑34c‑5p in U251 cells and with miR‑34c‑3p in U87 cells produced S‑phase arrest with G0/G1 reduction and induced cell apoptosis, but no significant changes were observed with miR‑34c‑5p transfection in U87 cells, normal or negative control groups. However, significant inhibition of glioma cell invasion was observed following transfection with miR‑34c‑3p and miR‑34c‑5p. Moreover, it was identified that miR‑34c‑3p overexpression reduced the expression of Notch pathway members, but miR‑34c‑5p overexpression did not. Therefore, these results suggest differential tumor suppressor roles for miR‑34c‑3p and miR‑34c‑5p and provide new insights into the role of miR‑34c in glioma, which includes tumor‑suppressing effects on proliferation, apoptosis and invasiveness.

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1	Wen PY and Kesari S: Malignant gliomas in adults. N Engl J Med. 359:492–507. 2008. View Article : Google Scholar : PubMed/NCBI
2	Fu LL, Wen X, Bao JK and Liu B: MicroRNA-modulated autophagic signaling networks in cancer. Int J Biochem Cell Biol. 44:733–736. 2012. View Article : Google Scholar : PubMed/NCBI
3	Lima RT, Busacca S, Almeida GM, Gaudino G, Fennell DA and Vasconcelos MH: MicroRNA regulation of core apoptosis pathways in cancer. Eur J Cancer. 47:163–174. 2011. View Article : Google Scholar : PubMed/NCBI
4	Lu J, Getz G, Miska EA, et al: MicroRNA expression profiles classify human cancers. Nature. 435:834–838. 2005. View Article : Google Scholar : PubMed/NCBI
5	Croce CM: Causes and consequences of microRNA dysregulation in cancer. Nat Rev Genet. 10:704–714. 2009. View Article : Google Scholar : PubMed/NCBI
6	Nan Y, Han L, Zhang A, et al: MiRNA-451 plays a role as tumor suppressor in human glioma cells. Brain Res. 1359:14–21. 2010. View Article : Google Scholar : PubMed/NCBI
7	Sana J, Hajduch M, Michalek J, Vyzula R and Slaby O: MicroRNAs and glioblastoma: roles in core signalling pathways and potential clinical implications. J Cell Mol Med. 15:1636–1644. 2011. View Article : Google Scholar : PubMed/NCBI
8	Cho WC: MicroRNAs in cancer - from research to therapy. Biochim Biophys Acta. 1805:209–217. 2010.PubMed/NCBI
9	Corney DC, Flesken-Nikitin A, Godwin AK, Wang W and Nikitin AY: MicroRNA-34b and MicroRNA-34c are targets of p53 and cooperate in control of cell proliferation and adhesion-independent growth. Cancer Res. 67:8433–8438. 2007. View Article : Google Scholar : PubMed/NCBI
10	He L, He X, Lim LP, et al: A microRNA component of the p53 tumour suppressor network. Nature. 447:1130–1134. 2007. View Article : Google Scholar : PubMed/NCBI
11	Cai KM, Bao XL, Kong XH, et al: Hsa-miR-34c suppresses growth and invasion of human laryngeal carcinoma cells via targeting c-Met. Int J Mol Med. 25:565–571. 2010.PubMed/NCBI
12	Landgraf P, Rusu M, Sheridan R, et al: A mammalian microRNA expression atlas based on small RNA library sequencing. Cell. 129:1401–1414. 2007. View Article : Google Scholar : PubMed/NCBI
13	Cannell IG, Kong YW, Johnston SJ, et al: p38 MAPK/MK2-mediated induction of miR-34c following DNA damage prevents Myc-dependent DNA replication. Proc Natl Acad Sci USA. 107:5375–5380. 2010. View Article : Google Scholar : PubMed/NCBI
14	López JA and Alvarez-Salas LM: Differential effects of miR-34c-3p and miR-34c-5p on SiHa cells proliferation apoptosis, migration and invasion. Biochem Biophys Res Commun. 409:513–519. 2011.PubMed/NCBI
15	Kumar B, Hovland AR, Prasad JE, et al: Establishment of human embryonic brain cell lines. In Vitro Cell Dev Biol Anim. 37:259–262. 2001. View Article : Google Scholar : PubMed/NCBI
16	Hagman Z, Larne O, Edsjö A, et al: miR-34c is downregulated in prostate cancer and exerts tumor suppressive functions. International journal of cancer. Int J Cancer. 127:2768–2776. 2010. View Article : Google Scholar : PubMed/NCBI
17	Pang RT, Leung CO, Ye TM, et al: MicroRNA-34a suppresses invasion through downregulation of Notch1 and Jagged1 in cervical carcinoma and choriocarcinoma cells. Carcinogenesis. 31:1037–1044. 2010. View Article : Google Scholar : PubMed/NCBI
18	Luan S, Sun L and Huang F: MicroRNA-34a: a novel tumor suppressor in p53-mutant glioma cell line U251. Arch Med Res. 41:67–74. 2010. View Article : Google Scholar : PubMed/NCBI
19	Ji Q, Hao X, Zhang M, et al: MicroRNA miR-34 inhibits human pancreatic cancer tumor-initiating cells. PloS One. 4:e68162009. View Article : Google Scholar : PubMed/NCBI
20	Tarasov V, Jung P, Verdoodt B, et al: Differential regulation of microRNAs by p53 revealed by massively parallel sequencing: miR-34a is a p53 target that induces apoptosis and G1-arrest. Cell Cycle. 6:1586–1593. 2007. View Article : Google Scholar : PubMed/NCBI
21	Christoffersen NR, Shalgi R, Frankel LB, et al: p53-independent upregulation of miR-34a during oncogene-induced senescence represses MYC. Cell Death Differ. 17:236–245. 2010. View Article : Google Scholar : PubMed/NCBI
22	Kumamoto K, Spillare EA, Fujita K, et al: Nutlin-3a activates p53 to both down-regulate inhibitor of growth 2 and up-regulate mir-34a, mir-34b, and mir-34c expression, and induce senescence. Cancer Res. 68:3193–3203. 2008. View Article : Google Scholar : PubMed/NCBI
23	Guessous F, Zhang Y, Kofman A, et al: microRNA-34a is tumor suppressive in brain tumors and glioma stem cells. Cell Cycle. 9:1031–1036. 2010. View Article : Google Scholar : PubMed/NCBI
24	Solecki DJ, Liu XL, Tomoda T, Fang Y and Hatten ME: Activated Notch2 signaling inhibits differentiation of cerebellar granule neuron precursors by maintaining proliferation. Neuron. 31:557–568. 2001. View Article : Google Scholar : PubMed/NCBI
25	Sivasankaran B, Degen M, Ghaffari A, et al: Tenascin-C is a novel RBPJkappa-induced target gene for Notch signaling in gliomas. Cancer Res. 69:458–465. 2009. View Article : Google Scholar : PubMed/NCBI
26	Fan X, Mikolaenko I, Elhassan I, et al: Notch1 and notch2 have opposite effects on embryonal brain tumor growth. Cancer Res. 64:7787–7793. 2004. View Article : Google Scholar : PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Differential effects of miR‑34c‑3p and miR‑34c‑5p on the proliferation, apoptosis and invasion of glioma cells

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