Abstract
MicroRNAs are important regulators of multiple cellular processes, and aberrant miRNA expression has been observed in human glioblastoma (GBM). The present study was to evaluate the level of miR-124 and signal transducer and activator of transcription 3 (STAT3) in GBM tissues and cells. We further investigated the molecular mechanisms of miR-124 and STAT3 in GBM cell lines U87 and U251. Here, we found that miR-124 expression was downregulated in GBM tissues and U87 and U251 cells (all p < 0.001) but not associated with blood routine (RBC, WBC count, etc.) and liver and renal function indicators (all p > 0.05). By contrast, STAT3 was upregulated. Furthermore, the expression of miR-124 was inversely proportional to that of STAT3 mRNA or protein (p = 0.013, p = 0.015, respectively). In vitro studies demonstrated that the overexpression of miR-124 played a suppressor role in the proliferation of U87 and U251 cells and promoted cell apoptosis. Luciferase reporter assays confirmed that miR-124 binding to the 3′-UTR regions of STAT3 inhibited the expression of STAT3 in U87 and U251 cells. However, the inhibitor of miR-124 promoted the expression of STAT3 and cell proliferation. In conclusion, our data suggest that miR-124 may have a potential role in treatment of GBM patients and that miR-124 is a novel regulator of invasiveness and tumorigenicity in GBM cells by targeting STAT3. The miR-124/STAT3 pathway may be a useful therapeutic agent in GBM patients.
Similar content being viewed by others
References
Jemal A, Siegel R, Xu J (2010) Cancer statistics, 2010. CA Cancer J Clin 60:277–300
Liao A, Shi R, Jiang Y, Tian S, Li P, Song F, et al. SDF-1/CXCR4 Axis Regulates Cell Cycle Progression and Epithelial-Mesenchymal Transition via Up-regulation of Survivin in Glioblastoma. Mol Neurobiol. 2014 Nov 25. [Epub ahead of print].
Lv Q, Zhang J, Yi Y, Huang Y, Wang Y, Wang Y et al (2015) Proliferating cell nuclear antigen has an association with prognosis and risks factors of cancer patients: a systematic review. Mol Neurobiol, PMID: 26558632, [Epub ahead of print]
Lv B, Yang X, Lv S, Wang L, Fan K, Shi R et al (2015) CXCR4 signaling induced epithelial-mesenchymal transition by PI3K/AKT and ERK pathways in glioblastoma. Mol Neurobiol 52(3):1263–8
Altieri R, Fontanella M, Agnoletti A, Panciani PP, Spena G, Crobeddu E et al (2014) Role of nitric oxide in glioblastoma therapy: another step to resolve the terrible puzzle? Transl Med UniSa 12:54–9
Yanokura M, Banno K, Iida M, Irie H, Umene K, Masuda K et al (2015) MicroRNAS in endometrial cancer: recent advances and potential clinical applications. EXCLI J 14:190–8
Das SS, Karmakar P, Nandi AK, Sanan-Mishra N (2015) Small RNA mediated regulation of seed germination. Front Plant Sci 6:828
Gardiner AS, Twiss JL, Perrone-Bizzozero NI (2015) Competing interactions of RNA-binding proteins, microRNAs, and their targets control neuronal development and function. Biomolecules 5(4):2903–18
He JF, Luo YM, Wan XH, Jiang D (2011) Biogenesis of MiRNA-154 and its role in biogenesis, the cell cycle, and apoptosis. J Biochem Mol Toxicol 25(6):404–8
Chabre O, Libe R, Assie G, Barreau O, Barreau O, Bertherat J et al (2013) Serum miR-483–5p and miR-124 are predictive of recurrence risk in adrenocortical cancer patients. Endocr Relat Cancer 20:579–594
Mao JH, Zhou RP, Peng AF, Liu ZL, Huang SH, Long XH et al (2012) microRNA-154 suppresses osteosarcoma cell invasion and migration in vitro by targeting FASN. Oncol Lett 4:1125–1129
Lv S, Sun B, Dai C, Shi R, Zhou X, Lv W et al (2015) The downregulation of microRNA-146a modulates TGF-β signaling pathways activity in glioblastoma. Mol Neurobiol 52(3):1257–62
Liu H, Ren G, Zhu L, Liu X, He X (2015) The upregulation of miRNA-146a inhibited biological behaviors of ESGBM through inhibition of IRS2. Tumour Biol 28 [Epub ahead of print]
Hsieh FC, Cheng G, Lin J (2005) Evaluation of potential Stat3-regulated genes in human breast cancer. Biochem Biophys Res Commun 335:292–299
Catlett-Falcone R, Landowski TH, Oshiro MM, Turkson J, Levitzki A, Savino R et al (1999) Constitutive activation of Stat3 signaling confers resistance to apoptosis in human U266 myeloma cells. Immunity 10:105–115
Grandis JR, Drenning SD, Zeng Q, Watkins SC, Melhem MF, Endo S et al (2000) Constitutive activation of Stat3 signaling abrogates apoptosis in squamous cell carcinogenesis in vivo. Proc Natl Acad Sci U S A 97:4227–4232
Yan X, Fraser M, Qiu Q, Tsang BK (2006) Over-expression of PTEN sensitizes human ovarian cancer cells to cisplatin-induced apoptosis in a p53-dependent manner. Gynecol Oncol 102:348–355
Epling-Burnette PK, Liu JH, Catlett-Falcone R, Turkson J, Oshiro M, Kothapalli R et al (2001) Inhibition of Stat3 signaling leads to apoptosis of leukemic large granular lymphocytes and decreased Mcl-1 expression. J Clin Invest 107:351–362
Zhao G, Zhang JG, Shi Y, Qin Q, Liu Y, Wang B et al (2013) MiR-130b is a prognostic marker and inhibits cell proliferation and invasion in pancreatic cancer through targeting STAT3. PLoS One 8(9), e73803
Acknowledgements
We thank all the patients who were willing to be recruited in this investigation.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Human tissue samples used in this study were obtained with written informed consent from the patients or their relatives. This study was approved by the Ethics Committee of Second Hospital of Hebei Medical University.
Conflicts of interest
None.
Additional information
This article has been retracted at the request of the Editor-in-Chief and the Publisher per the Committee on Publication Ethics guidelines. The article shows evidence of irregularities in authorship during the submission process, there is strong reason to believe that the peer review process was compromised and the authors have plagiarized parts from the following article:
Zhen Li, Hua Wang, Zhiqiang Wang, Hongbing Cai, MiR-195 inhibits the proliferation of human cervical cancer cells by directly targeting cyclin D1, Tumor Biol. (2016) 37:6457-6463, DOI 10.1007/s13277-015-4540-6, Received: 4 November 2015
As such the validity of the content of this article cannot be verified.
An erratum to this article is available at http://dx.doi.org/10.1007/s12035-017-0682-4.
About this article
Cite this article
Li, W., Huang, H., Su, J. et al. RETRACTED ARTICLE: miR-124 Acts as a Tumor Suppressor in Glioblastoma via the Inhibition of Signal Transducer and Activator of Transcription 3. Mol Neurobiol 54, 2555–2561 (2017). https://doi.org/10.1007/s12035-016-9852-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12035-016-9852-z