Abstract
Glioma is the most common intracranial malignant tumor. Cancer stem cells (CSCs) are resistant to chemotherapy and radiotherapy, and are closely related to cancer metastasis and recurrence. In this study, we aimed to explore the effect of miR-484 on glioma stemness and the underlying mechanism involved. miR-484 enhanced glioma tumor-initiating properties in vitro and in vivo. Moreover, miR-484 was shown to directly target MAP2, resulting in activation of ERK1/2 signaling and promotion of stemness in glioma. The ERK1/2 signaling facilitated the formation of a miR-484/MAP2/c-Myc positive feedback loop in glioma. High miR-484 expression predicted a poor prognosis for glioma patients, and high MAP2 expression predicted a good prognosis for glioma patients. Low miR-484 expression and high MAP2 expression was associated with the best prognosis in glioma. Our study suggests that miR-484 and MAP2 can be utilized as predictors for the clinical diagnosis and prognosis of glioma, and miR-484 and MAP2 are potential targets for the treatment of glioma.
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References
Ahmed Z et al (2015) Grb2 monomer-dimer equilibrium determines normal versus oncogenic function. Nat Commun 6:7354. https://doi.org/10.1038/ncomms8354
Batash R, Asna N, Schaffer P, Francis N, Schaffer M (2017) Glioblastoma multiforme, diagnosis and treatment. Recent Literature Rev Curr Med Chem 24:3002–3009. https://doi.org/10.2174/0929867324666170516123206
Bhat KM, Maddodi N, Shashikant C, Setaluri V (2006) Transcriptional regulation of human MAP2 gene in melanoma: role of neuronal bHLH factors and Notch1 signaling. Nucleic Acids Res 34:3819–3832. https://doi.org/10.1093/nar/gkl476
Blumcke I, Muller S, Buslei R, Riederer BM, Wiestler OD (2004) Microtubule-associated protein-2 immunoreactivity: a useful tool in the differential diagnosis of low-grade neuroepithelial tumors. Acta Neuropathol 108:89–96. https://doi.org/10.1007/s00401-004-0873-8
Deng Y, Zhu G, Luo H, Zhao S (2016) MicroRNA-203 As a stemness inhibitor of glioblastoma stem cells. Mol Cells 39:619–624. https://doi.org/10.14348/molcells.2016.0118
Dinsmore JH, Solomon F (1991) Inhibition of MAP2 expression affects both morphological and cell division phenotypes of neuronal differentiation. Cell 64:817–826
Fischer I, Shea TB, Sapirstein VS, Kosik KS (1986) Expression and distribution of microtubule-associated protein 2 (MAP2) in neuroblastoma and primary neuronal cells. Brain Res 390:99–109
Gambichler T, Rotterdam S, Radkowski K, Altmeyer P, Kreuter A (2009) Differential expression of microtubule-associated protein 2 in melanocytic skin lesions. Am J Clin Pathol 131:710–714. https://doi.org/10.1309/ajcpr84ulyvmnjhg
Hu Y, Xie H, Liu Y, Liu W, Liu M, Tang H (2017) miR-484 suppresses proliferation and epithelial-mesenchymal transition by targeting ZEB1 and SMAD2 in cervical cancer cells. Cancer Cell Int 17:36. https://doi.org/10.1186/s12935-017-0407-9
Kjersem JB, Ikdahl T, Lingjaerde OC, Guren T, Tveit KM, Kure EH (2014) Plasma microRNAs predicting clinical outcome in metastatic colorectal cancer patients receiving first-line oxaliplatin-based treatment. Mol Oncol 8:59–67. https://doi.org/10.1016/j.molonc.2013.09.001
Krishnan C, Higgins JP, West RB, Natkunam Y, Heerema-McKenney A, Arber DA (2009) Microtubule-associated protein-2 is a sensitive marker of primary and metastatic neuroblastoma. Am J Surg Pathol 33:1695–1704. https://doi.org/10.1097/PAS.0b013e3181b0ebdc
Le DH (2015) Network-based ranking methods for prediction of novel disease associated microRNAs. Comput Biol Chem 58:139–148. https://doi.org/10.1016/j.compbiolchem.2015.07.003
Li T, Ding ZL, Zheng YL, Wang W (2017) MiR-484 promotes non-small-cell lung cancer (NSCLC) progression through inhibiting Apaf-1 associated with the suppression of apoptosis. Biomed Pharmacother 96:153–164. https://doi.org/10.1016/j.biopha.2017.09.102
Lim RW, Halpain S (2000) Regulated association of microtubule-associated protein 2 (MAP2) with Src and Grb2: evidence for MAP2 as a scaffolding protein. J Biol Chem 275:20578–20587. https://doi.org/10.1074/jbc.M001887200
Lopez-Bertoni H, Lal B, Michelson N, Guerrero-Cazares H, Quinones-Hinojosa A, Li Y, Laterra J (2016) Epigenetic modulation of a miR-296-5p:HMGA1 axis regulates Sox2 expression and glioblastoma stem cells. Oncogene 35:4903–4913. https://doi.org/10.1038/onc.2016.22
Mei Q et al (2015) Methylation-induced loss of miR-484 in microsatellite-unstable colorectal cancer promotes both viability and IL-8 production via CD137L. J Pathol 236:165–174. https://doi.org/10.1002/path.4525
Naveen CR, Gaikwad S, Agrawal-Rajput R (2016) Berberine induces neuronal differentiation through inhibition of cancer stemness and epithelial-mesenchymal transition in neuroblastoma cells. Phytomedicine 23:736–744. https://doi.org/10.1016/j.phymed.2016.03.013
Pashaei E, Pashaei E, Ahmady M, Ozen M, Aydin N (2017) Meta-analysis of miRNA expression profiles for prostate cancer recurrence following radical prostatectomy. PLoS ONE 12:e0179543. https://doi.org/10.1371/journal.pone.0179543
Song Z et al (2010) Increased expression of MAP2 inhibits melanoma cell proliferation, invasion and tumor growth in vitro and in vivo. Exp Dermatol 19:958–964. https://doi.org/10.1111/j.1600-0625.2009.01020.x
Song H, Zhang Y, Liu N, Zhao S, Kong Y, Yuan L (2016) miR-92a-3p exerts various effects in glioma and glioma stem-like cells specifically targeting CDH1/beta-catenin and Notch-1/Akt signaling pathways. Int J Mol Sci. https://doi.org/10.3390/ijms17111799
Stokowy T et al (2016) Two-miRNA classifiers differentiate mutation-negative follicular thyroid carcinomas and follicular thyroid adenomas in fine needle aspirations with high specificity. Endocrine 54:440–447. https://doi.org/10.1007/s12020-016-1021-7
Sun XK et al (2017) Down-regulation of Noggin and miR-138 coordinately promote osteogenesis of mesenchymal stem cells. J Mol Histol 48:427–436. https://doi.org/10.1007/s10735-017-9740-5
Sung CO, Suh YL, Hong SC (2011) CD34 and microtubule-associated protein 2 expression in dysembryoplastic neuroepithelial tumours with an emphasis on dual expression in non-specific types. Histopathology 59:308–317. https://doi.org/10.1111/j.1365-2559.2011.03936.x
Takebe N et al (2015) Targeting Notch, Hedgehog, and Wnt pathways in cancer stem cells: clinical update. Nat Rev Clin Oncol 12:445–464. https://doi.org/10.1038/nrclinonc.2015.61
Tessitore A et al (2016) MicroRNA expression analysis in high fat diet-induced NAFLD-NASH-HCC progression: study on C57BL/6J mice. BMC Cancer 16:3. https://doi.org/10.1186/s12885-015-2007-1
Vecchione A et al (2013) A microRNA signature defines chemoresistance in ovarian cancer through modulation of angiogenesis. Proc Natl Acad Sci USA 110:9845–9850. https://doi.org/10.1073/pnas.1305472110
Wang K, Long B, Jiao JQ, Wang JX, Liu JP, Li Q, Li PF (2012) miR-484 regulates mitochondrial network through targeting Fis1. Nat Commun 3:781. https://doi.org/10.1038/ncomms1770
Yang Y et al (2016) Interferon-microRNA signalling drives liver precancerous lesion formation and hepatocarcinogenesis. Gut 65:1186–1201. https://doi.org/10.1136/gutjnl-2015-310318
Ye FG et al (2015) Cytidine deaminase axis modulated by miR-484 differentially regulates cell proliferation and chemoresistance in breast cancer. Cancer Res 75:1504–1515. https://doi.org/10.1158/0008-5472.can-14-2341
Zhao C et al (2016) Silencing of CtBP1 suppresses the migration in human glioma cells. J Mol Histol 47:297–304. https://doi.org/10.1007/s10735-016-9678-z
Zheng S, Shi L, Zhang Y, He T (2014) Expression of SNCG, MAP2, SDF-1 and CXCR4 in gastric adenocarcinoma and their clinical significance. Int J Clin Exp Pathol 7:6606–6615
Zhou DM, Sun Y, Li XH (2013) Diagnostic value of microtubule-associated protein-2 in small cell lung carcinoma: an analysis of 240 biopsy cases. J Pathol [Zhonghua bing li xue za zhi (Chinese)] 42:321–324. https://doi.org/10.3760/cma.j.issn.0529-5807.2013.05.007
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We thank Southern Medical University for the kind offer of patient tissues.
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Yi, R., Feng, J., Yang, S. et al. miR-484/MAP2/c-Myc-positive regulatory loop in glioma promotes tumor-initiating properties through ERK1/2 signaling. J Mol Hist 49, 209–218 (2018). https://doi.org/10.1007/s10735-018-9760-9
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DOI: https://doi.org/10.1007/s10735-018-9760-9