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Molecular Cancer
Published in: Molecular Cancer 1/2017

Open Access 01-12-2017 | Research

RETRACTED ARTICLE: Linc00152 promotes malignant progression of glioma stem cells by regulating miR-103a-3p/FEZF1/CDC25A pathway

Authors: Mingjun Yu, Yixue Xue, Jian Zheng, Xiaobai Liu, Hai Yu, Libo Liu, Zhen Li, Yunhui Liu

Published in: Molecular Cancer | Issue 1/2017

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Abstract

Background

Glioma is one of the most frequent intracranial malignant tumors. LncRNAs have been identified as new modulators in the origination and progression of glioma.

Methods

Quantitative real-time PCR were conducted to evaluate the expression of linc00152 and miRNA-103a-3p in glioma tissues and cells. Western blot were used to determine the expression of FEZF1 and CDC25A in glioma tissues and cells. Stable knockdown of linc00152 or over-expression of miR-103a-3p in glioma stem cells (GSCs) were established to explore the function of linc00152 and miR-103a-3p in GSCs. Further, luciferase reports were used to investigate the correlation between linc00152 and miR-103a-3p. Cell Counting Kit-8, transwell assays, and flow cytometry were used to investigate the function of linc00152 and miR-103a-3p in GSC malignant biological behaviors. ChIP assays were employed to ascertain the correlations between FEZF1 and CDC25A.

Results

Linc00152 was up-regulated in glioma tissues as well as in GSCs. Knockdown of linc00152 inhibited cell proliferation, migration and invasion, while promoted GSC apoptosis. Linc00152 regulated the malignant behavior of GSCs by binding to miR-103a-3p, which functions as a tumor suppressor. In addition, knockdown of linc00152 down-regulated forebrain embryonic zinc finger protein 1 (FEZF1), a direct target of miR-103a-3p which played an oncogenic role in GSCs. FEZF1 elevated promoter activities and up-regulated expression of the oncogenic gene cell division cycle 25A (CDC25A). CDC25A over-expression activated the PI3K/AKT pathways, which regulated the malignant behavior of GSCs.

Conclusions

Linc00152/miR-103a-3p/FEZF1/CDC25A axis plays a novel role in regulating the malignant behavior of GSCs, which may be a new potential therapeutic strategy for glioma therapy.
Appendix
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Literature
1.
Zheng J, Liu X, Xue Y, Gong W, Ma J, Xi Z, et al. TTBK2 circular RNA promotes glioma malignancy by regulating miR-217/HNF1beta/Derlin-1 pathway. J Hematol Oncol. 2017;10:52.PubMedPubMedCentralCrossRef
2.
Tso JL, Yang S, Menjivar JC, Yamada K, Zhang Y, Hong I, et al. Bone morphogenetic protein 7 sensitizes O6-methylguanine methyltransferase expressing-glioblastoma stem cells to clinically relevant dose of temozolomide. Mol Cancer. 2015;14:189.PubMedPubMedCentralCrossRef
3.
Bao S, Wu Q, McLendon RE, Hao Y, Shi Q, Hjelmeland AB, et al. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature. 2006;444:756–60.PubMedCrossRef
4.
Cheng P, Wang J, Waghmare I, Sartini S, Coviello V, Zhang Z, et al. FOXD1-ALDH1A3 signaling is a determinant for the self-renewal and Tumorigenicity of Mesenchymal Glioma stem cells. Cancer Res. 2016;76:7219–30.PubMedPubMedCentralCrossRef
5.
Zhang XQ, Leung GK. Long non-coding RNAs in glioma: functional roles and clinical perspectives. Neurochem Int. 2014;77:78–85.PubMedCrossRef
6.
Yao Y, Ma J, Xue Y, Wang P, Li Z, Liu J, et al. Knockdown of long non-coding RNA XIST exerts tumor-suppressive functions in human glioblastoma stem cells by up-regulating miR-152. Cancer Lett. 2015;359:75–86.PubMedCrossRef
7.
Perry RB, Ulitsky I. The functions of long noncoding RNAs in development and stem cells. Development. 2016;143:3882–94.PubMedCrossRef
8.
Chen WM, Huang MD, Sun DP, Kong R, Xu TP, Xia R, et al. Long intergenic non-coding RNA 00152 promotes tumor cell cycle progression by binding to EZH2 and repressing p15 and p21 in gastric cancer. Oncotarget. 2016;7:9773–87.PubMedPubMedCentralCrossRef
9.
Yue B, Cai D, Liu C, Fang C, Yan D. Linc00152 functions as a competing endogenous RNA to confer Oxaliplatin resistance and holds prognostic values in Colon cancer. Mol Ther. 2016;24:2064–77.PubMedPubMedCentralCrossRef
10.
Liu L, Bi N, Wu L, Ding X, Men Y, Zhou W, et al. MicroRNA-29c functions as a tumor suppressor by targeting VEGFA in lung adenocarcinoma. Mol Cancer. 2017;16:50.PubMedPubMedCentralCrossRef
11.
Zhang KL, Zhou X, Han L, Chen LY, Chen LC, Shi ZD, et al. MicroRNA-566 activates EGFR signaling and its inhibition sensitizes glioblastoma cells to nimotuzumab. Mol Cancer. 2014;13:63.PubMedPubMedCentralCrossRef
12.
Bignotti E, Calza S, Tassi RA, Zanotti L, Bandiera E, Sartori E, et al. Identification of stably expressed reference small non-coding RNAs for microRNA quantification in high-grade serous ovarian carcinoma tissues. J Cell Mol Med. 2016;20:2341–8.PubMedPubMedCentralCrossRef
13.
Shen S, Sun Q, Liang Z, Cui X, Ren X, Chen H, et al. A prognostic model of triple-negative breast cancer based on miR-27b-3p and node status. PLoS One. 2014;9:e100664.PubMedPubMedCentralCrossRef
14.
Vigneri P, Martorana F, Manzella L, Stella S. Biomarkers and prognostic factors for malignant pleural mesothelioma. Future Oncol. 2015;11:29–33.PubMedCrossRef
15.
Hamaya Y, Kuriyama S, Takai T, Yoshida K, Yamada T, Sugimoto M, et al. A distinct expression pattern of the long 3′-untranslated region dicer mRNA and its implications for posttranscriptional regulation in colorectal cancer. Clin Transl Gastroenterol. 2012;3:e17.PubMedPubMedCentralCrossRef
16.
17.
Eckler MJ, McKenna WL, Taghvaei S, McConnell SK, Chen B. Fezf1 and Fezf2 are required for olfactory development and sensory neuron identity. J Comp Neurol. 2011;519:1829–46.PubMedPubMedCentralCrossRef
18.
Song IS, Ha GH, Kim JM, Jeong SY, Lee HC, Kim YS, et al. Human ZNF312b oncogene is regulated by Sp1 binding to its promoter region through DNA demethylation and histone acetylation in gastric cancer. Int J Cancer. 2011;129:2124–33.PubMedCrossRef
19.
Galaktionov K, Lee AK, Eckstein J, Draetta G, Meckler J, Loda M, et al. CDC25 phosphatases as potential human oncogenes. Science. 1995;269:1575–7.PubMedCrossRef
20.
Sur S, Agrawal DK. Phosphatases and kinases regulating CDC25 activity in the cell cycle: clinical implications of CDC25 overexpression and potential treatment strategies. Mol Cell Biochem. 2016;416:33–46.PubMedPubMedCentralCrossRef
21.
Chen L, Zheng J, Yang N, Li H, Guo S. Genomic selection identifies vertebrate transcription factor Fezf2 binding sites and target genes. J Biol Chem. 2011;286:18641–9.PubMedPubMedCentralCrossRef
22.
Shimizu T, Hibi M. Formation and patterning of the forebrain and olfactory system by zinc-finger genes Fezf1 and Fezf2. Develop Growth Differ. 2009;51:221–31.CrossRef
23.
Li Y, Ji S, Fu LY, Jiang T, Wu D, Meng FD. Knockdown of cyclin-dependent kinase inhibitor-3 inhibits proliferation and invasion in human gastric cancer cells. Oncol Res. 2017;25:721–31.PubMedPubMedCentralCrossRef
24.
Zheng J, Liu X, Wang P, Xue Y, Ma J, Qu C, et al. CRNDE promotes malignant progression of Glioma by attenuating miR-384/PIWIL4/STAT3 Axis. Mol Ther. 2016;24:1199–215.PubMedPubMedCentralCrossRef
25.
Shimizu T, Nakazawa M, Kani S, Bae YK, Shimizu T, Kageyama R, et al. Zinc finger genes Fezf1 and Fezf2 control neuronal differentiation by repressing Hes5 expression in the forebrain. Development. 2010;137:1875–85.PubMedCrossRef
26.
Ma H, Chen J, Pan S, Dai J, Jin G, Hu Z, et al. Potentially functional polymorphisms in cell cycle genes and the survival of non-small cell lung cancer in a Chinese population. Lung Cancer. 2011;73:32–7.PubMedCrossRef
27.
Wu W, Fan YH, Kemp BL, Walsh G, Mao L. Overexpression of cdc25A and cdc25B is frequent in primary non-small cell lung cancer but is not associated with overexpression of c-myc. Cancer Res. 1998;58:4082–5.PubMed
28.
Zhao S, Wang Y, Guo T, Yu W, Li J, Tang Z, et al. YBX1 regulates tumor growth via CDC25a pathway in human lung adenocarcinoma. Oncotarget. 2016;7:82139–57.PubMedPubMedCentralCrossRef
29.
Brenner AK, Reikvam H, Lavecchia A, Bruserud O. Therapeutic targeting the cell division cycle 25 (CDC25) phosphatases in human acute myeloid leukemia--the possibility to target several kinases through inhibition of the various CDC25 isoforms. Molecules. 2014;19:18414–47.PubMedPubMedCentralCrossRef
30.
Yamashita Y, Kasugai I, Sato M, Tanuma N, Sato I, Nomura M, et al. CDC25A mRNA levels significantly correlate with Ki-67 expression in human glioma samples. J Neuro-Oncol. 2010;100:43–9.CrossRef
31.
Cai H, Xue Y, Liu W, Li Z, Hu Y, Li Z, et al. Overexpression of Roundabout4 predicts poor prognosis of primary glioma patients via correlating with microvessel density. J Neuro-Oncol. 2015;123:161–9.CrossRef
32.
Liu X, Chong Y, Tu Y, Liu N, Yue C, Qi Z, et al. CRM1/XPO1 is associated with clinical outcome in glioma and represents a therapeutic target by perturbing multiple core pathways. J Hematol Oncol. 2016;9:108.PubMedPubMedCentralCrossRef
33.
Alvarado AG, Thiagarajan PS, Mulkearns-Hubert EE, Silver DJ, Hale JS, Alban TJ, et al. Loss of TLR4 expression promotes glioblastoma stem cell stemness. Cancer Discov. 2017;7:246.
34.
Lee G, Auffinger B, Guo D, Hasan T, Deheeger M, Tobias AL, et al. Dedifferentiation of Glioma cells to Glioma stem-like cells by therapeutic stress-induced HIF signaling in the recurrent GBM model. Mol Cancer Ther. 2016;15:3064–76.PubMedPubMedCentralCrossRef
35.
Cai Q, Wang Z, Wang S, Weng M, Zhou D, Li C, et al. Long non-coding RNA LINC00152 promotes gallbladder cancer metastasis and epithelial-mesenchymal transition by regulating HIF-1alpha via miR-138. Open Biol. 2017; doi:10.​1098/​rsob.​160247.
36.
Zhao J, Liu Y, Zhang W, Zhou Z, Wu J, Cui P, et al. Long non-coding RNA Linc00152 is involved in cell cycle arrest, apoptosis, epithelial to mesenchymal transition, cell migration and invasion in gastric cancer. Cell Cycle. 2015;14:3112–23.PubMedPubMedCentralCrossRef
37.
Pang Q, Ge J, Shao Y, Sun W, Song H, Xia T, et al. Increased expression of long intergenic non-coding RNA LINC00152 in gastric cancer and its clinical significance. Tumour Biol. 2014;35:5441–7.PubMedCrossRef
38.
Zhao X, Wang P, Liu J, Zheng J, Liu Y, Chen J, et al. Gas5 exerts tumor-suppressive functions in human Glioma cells by targeting miR-222. Mol Ther. 2015;23:1899–911.PubMedPubMedCentralCrossRef
39.
Kim H, Yang JM, Jin Y, Jheon S, Kim K, Lee CT, et al. MicroRNA expression profiles and clinicopathological implications in lung adenocarcinoma according to EGFR, KRAS, and ALK status. Oncotarget. 2017;8:8484–98.PubMedCrossRef
40.
Serafin A, Foco L, Zanigni S, Blankenburg H, Picard A, Zanon A, et al. Overexpression of blood microRNAs 103a, 30b, and 29a in L-dopa-treated patients with PD. Neurology. 2015;84:645–53.PubMedCrossRef
41.
Hromadnikova I, Kotlabova K, Hympanova L, Krofta L. Gestational hypertension, preeclampsia and intrauterine growth restriction induce dysregulation of cardiovascular and cerebrovascular disease associated microRNAs in maternal whole peripheral blood. Thromb Res. 2016;137:126–40.PubMedCrossRef
42.
Zhang Y, Qu X, Li C, Fan Y, Che X, Wang X, et al. miR-103/107 modulates multidrug resistance in human gastric carcinoma by downregulating Cav-1. Tumour Biol. 2015;36:2277–85.PubMedCrossRef
43.
Zhong Z, Lv M, Chen J. Screening differential circular RNA expression profiles reveals the regulatory role of circTCF25-miR-103a-3p/miR-107-CDK6 pathway in bladder carcinoma. Sci Rep. 2016;6:30919.PubMedPubMedCentralCrossRef
44.
Song IS, Oh NS, Kim HT, Ha GH, Jeong SY, Kim JM, et al. Human ZNF312b promotes the progression of gastric cancer by transcriptional activation of the K-ras gene. Cancer Res. 2009;69:3131–9.PubMedCrossRef
45.
Iavarone A, Massague J. Repression of the CDK activator Cdc25A and cell-cycle arrest by cytokine TGF-beta in cells lacking the CDK inhibitor p15. Nature. 1997;387:417–22.PubMedCrossRef
46.
Boutros R, Lobjois V, Ducommun B. CDC25 phosphatases in cancer cells: key players? Good targets? Nat Rev Cancer. 2007;7:495–507.PubMedCrossRef
47.
Wang XQ, Zhu YQ, Lui KS, Cai Q, Lu P, Poon RT. Aberrant polo-like kinase 1-Cdc25A pathway in metastatic hepatocellular carcinoma. Clin Cancer Res. 2008;14:6813–20.PubMedCrossRef
48.
Wang P, Zou F, Zhang X, Li H, Dulak A, Tomko RJ Jr, et al. microRNA-21 negatively regulates Cdc25A and cell cycle progression in colon cancer cells. Cancer Res. 2009;69:8157–65.PubMedPubMedCentralCrossRef
49.
Liang J, Cao R, Zhang Y, Xia Y, Zheng Y, Li X, et al. PKM2 dephosphorylation by Cdc25A promotes the Warburg effect and tumorigenesis. Nat Commun. 2016;7:12431.PubMedPubMedCentralCrossRef
50.
Lu Y, Li F, Xu T, Sun J. miRNA-497 negatively regulates the growth and motility of Chondrosarcoma cells by targeting Cdc25A. Oncol Res. 2016;23:155–63.PubMedPubMedCentralCrossRef
51.
Zanotto-Filho A, Goncalves RM, Klafke K, de Souza PO, Dillenburg FC, Carro L, et al. Inflammatory landscape of human brain tumors reveals an NFkappaB dependent cytokine pathway associated with mesenchymal glioblastoma. Cancer Lett. 2017;390:176–87.PubMedCrossRef
52.
Nawaz Z, Patil V, Paul Y, Hegde AS, Arivazhagan A, Santosh V, et al. PI3 kinase pathway regulated miRNome in glioblastoma: identification of miR-326 as a tumour suppressor miRNA. Mol Cancer. 2016;15(1):74.PubMedPubMedCentralCrossRef
53.
Lin F, de Gooijer MC, Hanekamp D, Chandrasekaran G, Buil LC, Thota N, et al. PI3K-mTOR pathway inhibition exhibits efficacy against high-grade Glioma in clinically relevant mouse models. Clin Cancer Res. 2017;23(5):1286–98.PubMedCrossRef
54.
Ciceroni C, Bonelli M, Mastrantoni E, Niccolini C, Laurenza M, Larocca LM, et al. Type-3 metabotropic glutamate receptors regulate chemoresistance in glioma stem cells, and their levels are inversely related to survival in patients with malignant gliomas. Cell Death Differ. 2013;20(3):396–407.PubMedCrossRef
55.
Zhou W, Liu L, Xue Y, Zheng J, Liu X, Ma J, et al. Combination of endothelial-Monocyte-activating polypeptide-II with Temozolomide suppress malignant biological behaviors of human Glioblastoma stem cells via miR-590-3p/MACC1 inhibiting PI3K/AKT/mTOR signal pathway. Front Mol Neurosci. 2017;10:68.PubMedPubMedCentralCrossRef
56.
Ma J, Yao Y, Wang P, Liu Y, Zhao L, Li Z, et al. MiR-152 functions as a tumor suppressor in glioblastoma stem cells by targeting Kruppel-like factor 4. Cancer Lett. 2014;355:85–95.PubMedCrossRef
57.
Gong W, Zheng J, Liu X, Ma J, Liu Y, Xue Y. Knockdown of NEAT1 restrained the malignant progression of glioma stem cells by activating microRNA let-7e. Oncotarget. 2016;7(38):62208–23.PubMedPubMedCentralCrossRef
Metadata
Title
RETRACTED ARTICLE: Linc00152 promotes malignant progression of glioma stem cells by regulating miR-103a-3p/FEZF1/CDC25A pathway
Authors
Mingjun Yu
Yixue Xue
Jian Zheng
Xiaobai Liu
Hai Yu
Libo Liu
Zhen Li
Yunhui Liu
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2017
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/s12943-017-0677-9

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