miR-218-5p inhibits the stem cell properties and invasive ability of the A2B5+CD133- subgroup of human glioma stem cells Retraction in /10.3892/or.2022.8383

Wu,Zhiwu; Han,Yong; Li,Yanyan; Li,Xuetao; Sun,Ting; Chen,Guilin; Huang,Yulun; Zhou,Youxin; Du,Ziwei

doi:10.3892/or.2015.4418

miR-218-5p inhibits the stem cell properties and invasive ability of the A2B5+CD133- subgroup of human glioma stem cells

Retraction in: /10.3892/or.2022.8383

Authors:
- Zhiwu Wu
- Yong Han
- Yanyan Li
- Xuetao Li
- Ting Sun
- Guilin Chen
- Yulun Huang
- Youxin Zhou
- Ziwei Du
View Affiliations

Affiliations: Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China
Published online on: November 13, 2015 https://doi.org/10.3892/or.2015.4418
Pages: 869-877

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

MicroRNAs (miRs) act as oncogenes or tumor-suppressor genes, and regulate the proliferation, apoptosis, invasion, differentiation, angiogenesis and behavior of glioma stem cells, which are important in glioma development and recurrence. The present study was performed to investigate the impact of miR-218-5p on stem cell properties and invasive ability of the A2B5+CD133- human glioma stem cell subgroup. qRT-PCR was used to detect miR-218-5p expression in non-cancerous brain and human glioma tissues, human glioma cell lines and human glioma stem cell lines. Lentivirus vectors encoding miR-218-5p and anti-miR-218-5p were constructed and stably transfected into A2B5+CD133- SHG-139s cells. Neurosphere formation Cell Counting Kit-8 (CCK-8) and Transwell assays, immunofluorescence and qRT-PCR analyses were used to explore the role of miR-218-5p in SHG-139s cells. qRT-PCR analysis showed that miR-218-5p expression was lower in human glioma tissues and cells than in non-cancerous brain tissues and normal human astrocyte cells, and lower in A2B5+CD133- (SHG-139s) cells than in CD133+ (SU2 and U87s) cells. The CCK-8 assay demonstrated that the growth curve was significantly inhibited in the miR-218-5p-SHG-139s cells compared to the miR-control, blank and anti-miR‑218-5p groups. The neurosphere formation assay indicated that upregulation of miR‑218-5p expression inhibited SHG-139s neurosphere formation. Immunofluorescence staining and qRT-PCR showed that miR-218-5p reduced stem cell marker (A2B5, nestin, PLAGL2, ALDH1 and Sox2) expression compared with the controls; however, immunofluorescence staining analysis showed that upregulation of miR-218-5p expression led to no difference in CD133 expression. miR‑218-5p reduced SHG-139s cell invasiveness in the Transwell assay and reduced MMP9 expression as detected in qRT-PCR and immunofluorescence analyses. All differences were statistically significant. miR-218-5p expression was lower in human glioma tissues, cells and the A2B5+CD133- human glioma stem cell subgroup. miR-218-5p may be a tumor-suppressor gene in glioma that functions by upregulating miR-218-5p expression, which inhibits the stem cell properties and invasive properties of SHG-139s cells.

View Figures

View References

1	Furnari FB, Fenton T, Bachoo RM, Mukasa A, Stommel JM, Stegh A, Hahn WC, Ligon KL, Louis DN, Brennan C, et al: Malignant astrocytic glioma: Genetics, biology, and paths to treatment. Genes Dev. 21:2683–2710. 2007. View Article : Google Scholar : PubMed/NCBI
2	Wen PY and Kesari S: Malignant gliomas in adults. N Engl J Med. 359:492–507. 2008. View Article : Google Scholar : PubMed/NCBI
3	Reya T, Morrison SJ, Clarke MF and Weissman IL: Stem cells, cancer, and cancer stem cells. Nature. 414:105–111. 2001. View Article : Google Scholar : PubMed/NCBI
4	Hadjipanayis CG and Van Meir EG: Brain cancer propagating cells: Biology, genetics and targeted therapies. Trends Mol Med. 15:519–530. 2009. View Article : Google Scholar : PubMed/NCBI
5	Wang J, Sakariassen PO, Tsinkalovsky O, Immervoll H, Bøe SO, Svendsen A, Prestegarden L, Røsland G, Thorsen F, Stuhr L, et al: CD133 negative glioma cells form tumors in nude rats and give rise to CD133 positive cells. Int J Cancer. 122:761–768. 2008. View Article : Google Scholar
6	Beier D, Hau P, Proescholdt M, Lohmeier A, Wischhusen J, Oefner PJ, Aigner L, Brawanski A, Bogdahn U and Beier CP: CD133⁺ and CD133⁻ glioblastoma-derived cancer stem cells show differential growth characteristics and molecular profiles. Cancer Res. 67:4010–4015. 2007. View Article : Google Scholar : PubMed/NCBI
7	Calin GA and Croce CM: MicroRNA signatures in human cancers. Nat Rev Cancer. 6:857–866. 2006. View Article : Google Scholar : PubMed/NCBI
8	Nicoloso MS, Spizzo R, Shimizu M, Rossi S and Calin GA: MicroRNAs - the micro steering wheel of tumour metastases. Nat Rev Cancer. 9:293–302. 2009. View Article : Google Scholar : PubMed/NCBI
9	Godlewski J, Newton HB, Chiocca EA and Lawler SE: MicroRNAs and glioblastoma; the stem cell connection. Cell Death Differ. 17:221–228. 2010. View Article : Google Scholar
10	Li Y, Guessous F, Zhang Y, Dipierro C, Kefas B, Johnson E, Marcinkiewicz L, Jiang J, Yang Y, Schmittgen TD, et al: MicroRNA-34a inhibits glioblastoma growth by targeting multiple oncogenes. Cancer Res. 69:7569–7576. 2009. View Article : Google Scholar : PubMed/NCBI
11	Zhang Y, Dutta A and Abounader R: The role of microRNAs in glioma initiation and progression. Front Biosci. 17:700–712. 2012. View Article : Google Scholar
12	Guessous F, Zhang Y, Kofman A, Catania A, Li Y, Schiff D, Purow B and Abounader R: microRNA-34a is tumor suppressive in brain tumors and glioma stem cells. Cell Cycle. 9:1031–1036. 2010. View Article : Google Scholar : PubMed/NCBI
13	Yang TQ, Lu XJ, Wu TF, Ding DD, Zhao ZH, Chen GL, Xie XS, Li B, Wei YX, Guo LC, et al: MicroRNA-16 inhibits glioma cell growth and invasion through suppression of BCL2 and the nuclear factor-κB1/MMP9 signaling pathway. Cancer Sci. 105:265–271. 2014. View Article : Google Scholar : PubMed/NCBI
14	Sun B, Pu B, Chu D, Chu X, Li W and Wei D: MicroRNA-650 expression in glioma is associated with prognosis of patients. J Neurooncol. 115:375–380. 2013. View Article : Google Scholar : PubMed/NCBI
15	Bier A, Giladi N, Kronfeld N, Lee HK, Cazacu S, Finniss S, Xiang C, Poisson L, deCarvalho AC, Slavin S, et al: MicroRNA-137 is downregulated in glioblastoma and inhibits the stemness of glioma stem cells by targeting RTVP-1. Oncotarget. 4:665–676. 2013. View Article : Google Scholar : PubMed/NCBI
16	Guo P, Lan J, Ge J, Nie Q, Guo L, Qiu Y and Mao Q: MiR-26a enhances the radiosensitivity of glioblastoma multiforme cells through targeting of ataxia-telangiectasia mutated. Exp Cell Res. 320:200–208. 2014. View Article : Google Scholar
17	Fan YC, Mei PJ, Chen C, Miao FA, Zhang H and Li ZL: MiR-29c inhibits glioma cell proliferation, migration, invasion and angiogenesis. J Neurooncol. 115:179–188. 2013. View Article : Google Scholar : PubMed/NCBI
18	Xia H, Yan Y, Hu M, Wang Y, Wang Y, Dai Y, Chen J, Di G, Chen X and Jiang X: MiR-218 sensitizes glioma cells to apoptosis and inhibits tumorigenicity by regulating ECOP-mediated suppression of NF-κB activity. Neuro Oncol. 15:413–422. 2013. View Article : Google Scholar
19	Song L, Huang Q, Chen K, Liu L, Lin C, Dai T, Yu C, Wu Z and Li J: miR-218 inhibits the invasive ability of glioma cells by direct downregulation of IKK-β. Biochem Biophys Res Commun. 402:135–140. 2010. View Article : Google Scholar : PubMed/NCBI
20	Liu Y, Yan W, Zhang W, Chen L, You G, Bao Z, Wang Y, Wang H, Kang C and Jiang T: miR-218 reverses high invasiveness of glioblastoma cells by targeting the oncogenic transcription factor LEF1. Oncol Rep. 28:1013–1021. 2012.PubMed/NCBI
21	Rao JS: Molecular mechanisms of glioma invasiveness: The role of proteases. Nat Rev Cancer. 3:489–501. 2003. View Article : Google Scholar : PubMed/NCBI
22	Wu JT and Kral JG: The NF-kappaB/IkappaB signaling system: A molecular target in breast cancer therapy. J Surg Res. 123:158–169. 2005. View Article : Google Scholar : PubMed/NCBI
23	Forsyth PA, Wong H, Laing TD, Rewcastle NB, Morris DG, Muzik H, Leco KJ, Johnston RN, Brasher PM, Sutherland G, et al: Gelatinase-A (MMP-2), gelatinase-B (MMP-9) and membrane type matrix metalloproteinase-1 (MT1-MMP) are involved in different aspects of the pathophysiology of malignant gliomas. Br J Cancer. 79:1828–1835. 1999. View Article : Google Scholar
24	Tu Y, Gao X, Li G, Fu H, Cui D, Liu H, Jin W and Zhang Y: MicroRNA-218 inhibits glioma invasion, migration, proliferation, and cancer stem-like cell self-renewal by targeting the polycomb group gene Bmi1. Cancer Res. 73:6046–6055. 2013. View Article : Google Scholar
25	Li Y, Wang H, Sun T, Chen J, Guo L, Shen H, Du Z and Zhou Y: Biological characteristics of a new human glioma cell line transformed into A2B5⁺ stem cells. Mol Cancer. 14:752015. View Article : Google Scholar
26	Lomonaco SL, Finniss S, Xiang C, Lee HK, Jiang W, Lemke N, Rempel SA, Mikkelsen T and Brodie C: Cilengitide induces autophagy-mediated cell death in glioma cells. Neuro Oncol. 13:857–865. 2011. View Article : Google Scholar : PubMed/NCBI
27	Gey GO, Bang FB and Gey MK: Responses of a variety of normal and malignant cells to continuous cultivation, and some practical applications of these responses to problems in the biology of disease. Ann NY Acad Sci. 58:976–999. 1954. View Article : Google Scholar : PubMed/NCBI
28	Ogden AT, Waziri AE, Lochhead RA, Fusco D, Lopez K, Ellis JA, Kang J, Assanah M, McKhann GM, Sisti MB, et al: Identification of A2B5⁺CD133⁻ tumor-initiating cells in adult human gliomas. Neurosurgery. 62:505–515. 2008. View Article : Google Scholar
29	Tchoghandjian A, Baeza N, Colin C, Cayre M, Metellus P, Beclin C, Ouafik L and Figarella-Branger D: A2B5 cells from human glioblastoma have cancer stem cell properties. Brain Pathol. 20:211–221. 2010. View Article : Google Scholar
30	Takeshima T, Johnston JM and Commissiong JW: Oligodendrocyte-type-2 astrocyte (O-2A) progenitors increase the survival of rat mesencephalic, dopaminergic neurons from death induced by serum deprivation. Neurosci Lett. 166:178–182. 1994. View Article : Google Scholar : PubMed/NCBI
31	Piepmeier JM, Fried I and Makuch R: Low-grade astrocytomas may arise from different astrocyte lineages. Neurosurgery. 33:627–632. 1993. View Article : Google Scholar : PubMed/NCBI
32	Bishop M and de la Monte SM: Dual lineage of astrocytomas. Am J Pathol. 135:517–527. 1989.PubMed/NCBI
33	Zhang B, Sun J, Yu SP, Chen C, Liu B, Liu ZF, Ren BC, Ming HL and Yang XJ: Rac1⁺ cells distributed in accordance with CD 133⁺ cells in glioblastomas and the elevated invasiveness of CD 133⁺ glioma cells with higher Rac1 activity. Chin Med J. 125:4344–4348. 2012.
34	Huang Q, Zhang QB, Dong J, Wu YY, Shen YT, Zhao YD, Zhu YD, Diao Y, Wang AD and Lan Q: Glioma stem cells are more aggressive in recurrent tumors with malignant progression than in the primary tumor, and both can be maintained long-term in vitro. BMC Cancer. 8:3042008. View Article : Google Scholar : PubMed/NCBI