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RETRACTED ARTICLE: Effects of microRNA-21 on Nerve Cell Regeneration and Neural Function Recovery in Diabetes Mellitus Combined with Cerebral Infarction Rats by Targeting PDCD4

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This article was retracted on 22 February 2021

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Abstract

We aimed to determine the effect and mechanism of microRNA-21 (miR-21) on nerve cell regeneration and nerve functional recovery in diabetes mellitus combined with cerebral infarction (DM + CI) rats by targeting PDCD4. A total of 125 male Wistar rats were selected for DM + CI rat model construction and assigned into the blank, miR-21 mimics, mimics control, miR-21 inhibitor, inhibitor control, miR-21 inhibitor + si-PDCD4 and si-PDCD4 groups. And, 20 healthy rats were selected for the normal group. Triphenylterazolium chloride (TTC) staining and HE staining were used for determination of the area of CI and pathological changes, respectively. Behaviors of rats in the eight groups were determined by forelimb placement test and balance beam walking test. Immunohistochemical staining, double immunofluorescence staining assay, Western blotting, and qRT-PCR were used to detect expressions of miR-21, PDCD4, HNA, Nestin, NeuN, β-III-Tub, PTEN, FasL, and GFAP. DNA laddering and TUNEL staining was used for cell apoptosis. TTC and HE staining confirmed that 87.5% rats were induced into CI + DM models successfully. Results of forelimb placement test and balance beam walking test showed that miR-21 mimics, and si-PCDC4 improved the nerve defect of model rats. Comparing with the blank group at the same time, rats in the miR-21 inhibitor group displayed significant decrease in the forelimb placement test score, significant increase in the balance beam walking test score, and exacerbation of nerve defect, while rats in the miR-21 mimics and si-PCDC4 groups displayed significant increase in forelimb placement test score and significant decrease in the balance beam walking test score and improvement of nerve defect situation. The HNA, Nestin, and PDCD4 expressions were decreased and the NeuN, β-III-Tub, and GFAP expressions were increased in the miR-21 mimics and si-PDCD4 groups comparing with the blank group. The results of miR-21 inhibitor group were on the contrary. In comparison to the blank group, the miR-21 mimics group and the si-PDCD4 had lower miR-21 expressions and higher expressions of PDCD4, PTEN, and FasL, while the miR-21 inhibitor group was in the opposite trend. The results of qRT-PCR were the same with Western blotting. The expressions of fluorescence in other groups were higher than the normal group; compared with the blank group, the miR-21 mimics group and the si-PDCD4 group had lower fluorescence expression and DNA ladder. However, the fluorescence expressions and DNA ladder of miR-21 inhibitor group increased markedly in contrast with the blank group. Comparing with the blank group, BrdU+/DEX+ fluorescence intensity significantly enhanced in the miR-21 mimics and si-PDCD4 groups and significantly reduced in the miR-21 inhibitor group. And, comparing with the blank group, in the miR-21 mimics group, the signal strength of luciferase carrying the wild-type PDCD4 was reduced by 25%. The present studies demonstrated that miR-21 could promote the nerve cell regeneration, suppress apoptosis of nerve cells in DM + CI rats and improves the nerve defect situation of DM + CI rats by inhibiting PDCD4.

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References

  1. Okwechime IO, Roberson S, Odoi A (2015) Prevalence and predictors of pre-diabetes and diabetes among adults 18 years or older in Florida: a multinomial logistic modeling approach. PLoS One 10(12):e0145781

    Article  Google Scholar 

  2. Ashcroft FM, Rorsman P (2012) Diabetes mellitus and the beta cell: the last ten years. Cell 148(6):1160–1171

    Article  CAS  Google Scholar 

  3. Mingrone G, Panunzi S, De Gaetano A, Guidone C, Iaconelli A, Leccesi L, Nanni G, Pomp A et al (2012) Bariatric surgery versus conventional medical therapy for type 2 diabetes. N Engl J Med 366(17):1577–1585

    Article  CAS  Google Scholar 

  4. Jannat S, Bhowmik NB, Alam D (2015) Clinical profile of ischemic stroke in type 2 diabetic patients: experience in a tertiary care hospital [J]. Birdem Medical Journal 5(2):88–91

    Article  Google Scholar 

  5. Bevilacqua M, Dominguez LJ, Barrella M, Barbagallo M (2007) Induction of vascular endothelial growth factor release by transcutaneous frequency modulated neural stimulation in diabetic polyneuropathy. J Endocrinol Investig 30(11):944–947

    Article  CAS  Google Scholar 

  6. Higashi Y (2009) Edaravone for the treatment of acute cerebral infarction: role of endothelium-derived nitric oxide and oxidative stress. Expert Opin Pharmacother 10(2):323–331

    Article  CAS  Google Scholar 

  7. Liu G, Friggeri A, Yang Y, Milosevic J, Ding Q, Thannickal VJ, Kaminski N, Abraham E (2010) miR-21 mediates fibrogenic activation of pulmonary fibroblasts and lung fibrosis. J Exp Med 207(8):1589–1597

    Article  CAS  Google Scholar 

  8. Hu A, Huang JJ, Xu WH, Jin XJ, Li JP, Tang YJ, Huang XF, Cui HJ et al (2014) miR-21 and miR-375 microRNAs as candidate diagnostic biomarkers in squamous cell carcinoma of the larynx: association with patient survival. Am J Transl Res 6(5):604–613

    PubMed  PubMed Central  Google Scholar 

  9. Cheng Y, Zhu P, Yang J, Liu X, Dong S, Wang X, Chun B, Zhuang J et al (2010) Ischaemic preconditioning-regulated miR-21 protects heart against ischaemia/reperfusion injury via anti-apoptosis through its target PDCD4. Cardiovasc Res 87(3):431–439

    Article  CAS  Google Scholar 

  10. Pratheeshkumar, P., Y.O. Son, S.P. Divya, L. Wang, L. Turcios, R.V. Roy, J.A. Hitron, D. Kim, J. Dai, P. Asha, Z. Zhang, and X. Shi (2016) Quercetin inhibits Cr(VI)-induced malignant cell transformation by targeting miR-21-PDCD4 signaling pathway. Oncotarget

  11. Pratheeshkumar, P., Y.O. Son, S.P. Divya, L. Turcios, R.V. Roy, J.A. Hitron, L. Wang, D. Kim, J. Dai, P. Asha, Z. Zhang, and X. Shi (2016) Hexavalent chromium induces malignant transformation of human lung bronchial epithelial cells via ROS-dependent activation of miR-21-PDCD4 signaling. Oncotarget

  12. Feeney DM, Gonzalez A, Law WA (1982) Amphetamine, haloperidol, and experience interact to affect rate of recovery after motor cortex injury. Science 217(4562):855–857

    Article  CAS  Google Scholar 

  13. Kapoor I, Kanaujiya J, Kumar Y, Thota JR, Bhatt ML, Chattopadhyay N, Sanyal S, Trivedi AK (2016) Proteomic discovery of MNT as a novel interacting partner of E3 ubiquitin ligase E6AP and a key mediator of myeloid differentiation. Oncotarget 7(7):7640–7656

    Article  Google Scholar 

  14. Charkiewicz R, Pilz L, Sulewska A, Kozlowski M, Niklinska W, Moniuszko M, Reszec J, Manegold C et al (2016) Validation for histology-driven diagnosis in non-small cell lung cancer using hsa-miR-205 and hsa-miR-21 expression by two different normalization strategies. Int J Cancer 138(3):689–697

    Article  CAS  Google Scholar 

  15. Steffensen R, Baech J, Nielsen KR (2015) Allelic discrimination by TaqMan-PCR for genotyping of human neutrophil antigens. Methods Mol Biol 1310:205–212

    Article  Google Scholar 

  16. Wu D, Raafat A, Pak E, Clemens S, Murashov AK (2012) Dicer-microRNA pathway is critical for peripheral nerve regeneration and functional recovery in vivo and regenerative axonogenesis in vitro. Exp Neurol 233(1):555–565

    Article  CAS  Google Scholar 

  17. Asangani IA, Rasheed SA, Nikolova DA, Leupold JH, Colburn NH, Post S, Allgayer H (2008) MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer. Oncogene 27(15):2128–2136

    Article  CAS  Google Scholar 

  18. Sheedy FJ, Palsson-McDermott E, Hennessy EJ, Martin C, O'Leary JJ, Ruan Q, Johnson DS, Chen Y et al (2010) Negative regulation of TLR4 via targeting of the proinflammatory tumor suppressor PDCD4 by the microRNA miR-21. Nat Immunol 11(2):141–147

    Article  CAS  Google Scholar 

  19. Motoyama K, Inoue H, Mimori K, Tanaka F, Kojima K, Uetake H, Sugihara K, Mori M (2010) Clinicopathological and prognostic significance of PDCD4 and microRNA-21 in human gastric cancer. Int J Oncol 36(5):1089–1095

    CAS  PubMed  Google Scholar 

  20. Najafi Z, Sharifi M, Javadi G (2015) Degradation of miR-21 induces apoptosis and inhibits cell proliferation in human hepatocellular carcinoma. Cancer Gene Ther 22(11):530–535

    Article  CAS  Google Scholar 

  21. Waters LC, Strong SL, Ferlemann E, Oka O, Muskett FW, Veverka V, Banerjee S, Schmedt T et al (2011) Structure of the tandem MA-3 region of Pdcd4 protein and characterization of its interactions with eIF4A and eIF4G: molecular mechanisms of a tumor suppressor. J Biol Chem 286(19):17270–17280

    Article  CAS  Google Scholar 

  22. Wang Q, Zhang Y, Yang HS (2012) Pdcd4 knockdown up-regulates MAP4K1 expression and activation of AP-1 dependent transcription through c-Myc. Biochim Biophys Acta 1823(10):1807–1814

    Article  CAS  Google Scholar 

  23. Liu G, Keeler BE, Zhukareva V, Houle JD (2010) Cycling exercise affects the expression of apoptosis-associated microRNAs after spinal cord injury in rats. Exp Neurol 226(1):200–206

    Article  CAS  Google Scholar 

  24. Yin, K., M. Liu, M. Zhang, F. Wang, M. Fen, Z. Liu, Y. Yuan, S. Gao, L. Yang, W. Zhang, J. Zhang, B. Guo, J. Xu, H. Liang, X. Chen, and W. Guan (2016) miR-208a-3p suppresses cell apoptosis by targeting PDCD4 in gastric cancer. Oncotarget

  25. Mao, X.H., M. Chen, Y. Wang, P.G. Cui, S.B. Liu, and Z.Y. Xu (2016) MicroRNA-21 regulates the ERK/NF-kappaB signaling pathway to affect the proliferation, migration, and apoptosis of human melanoma A375 cells by targeting SPRY1, PDCD4, and PTEN. Mol Carcinog

  26. Bonci D, De Maria R (2016) miR-15/miR-16 loss, miR-21 upregulation, or deregulation of their target genes predicts poor prognosis in prostate cancer patients. Mol Cell Oncol 3(4):e1109744

    Article  Google Scholar 

  27. Li, C., L. Song, Z. Zhang, X.X. Bai, M.F. Cui, and L.J. Ma (2016) MicroRNA-21 promotes TGF-beta1-induced epithelial-mesenchymal transition in gastric cancer through up-regulating PTEN expression. Oncotarget

  28. Lasithiotaki, I., E. Tsitoura, A. Koutsopoulos, E. Lagoudaki, C. Koutoulaki, G. Pitsidianakis, D.A. Spandidos, N.M. Siafakas, G. Sourvinos, and K.M. Antoniou (2016) Aberrant expression of miR-21, miR-376c and miR-145 and their target host genes in Merkel cell polyomavirus-positive non-small cell lung cancer. Oncotarget

  29. Ni Y, Zhang K, Liu X, Yang T, Wang B, Fu L, A L, Zhou Y (2014) miR-21 promotes the differentiation of hair follicle-derived neural crest stem cells into Schwann cells. Neural Regen Res 9(8):828–836

    Article  CAS  Google Scholar 

  30. Strickland IT, Richards L, Holmes FE, Wynick D, Uney JB, Wong LF (2011) Axotomy-induced miR-21 promotes axon growth in adult dorsal root ganglion neurons. PLoS One 6(8):e23423

    Article  CAS  Google Scholar 

  31. Zhao, Y. and Z. Ma (2016) Swimming training affects apoptosis-related microRNAs and reduces cardiac apoptosis in mice. Gen Physiol Biophys

  32. Zhu Q, Wang Z, Hu Y, Li J, Li X, Zhou L, Huang Y (2012) miR-21 promotes migration and invasion by the miR-21-PDCD4-AP-1 feedback loop in human hepatocellular carcinoma. Oncol Rep 27(5):1660–1668

    CAS  PubMed  Google Scholar 

  33. Ahmed MI, Mardaryev AN, Lewis CJ, Sharov AA, Botchkareva NV (2011) MicroRNA-21 is an important downstream component of BMP signalling in epidermal keratinocytes. J Cell Sci 124(Pt 20):3399–3404

    Article  CAS  Google Scholar 

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Acknowledgements

We would like to give our sincere appreciation to the reviewers for their helpful comments on this article.

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Authors and Affiliations

  1. Department of Neurosurgery, The First Hospital of Jilin University, No. 71, Xinmin Road, Chaoyang District, Changchun, 130021, Jilin Province, People’s Republic of China

    Yun-Bao Guo & Jin-Lu Yu

  2. Department of Radiology, The First Hospital of Jilin University, No. 71, Xinmin Road, Chaoyang District, Changchun, 130021, People’s Republic of China

    Tie-Feng Ji & Hong-Wei Zhou

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  1. Yun-Bao Guo
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Correspondence to Jin-Lu Yu.

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This article has been retracted. Please see the retraction notice for more detail: https://doi.org/10.1007/s12035-021-02334-9

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Guo, YB., Ji, TF., Zhou, HW. et al. RETRACTED ARTICLE: Effects of microRNA-21 on Nerve Cell Regeneration and Neural Function Recovery in Diabetes Mellitus Combined with Cerebral Infarction Rats by Targeting PDCD4. Mol Neurobiol 55, 2494–2505 (2018). https://doi.org/10.1007/s12035-017-0484-8

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  • DOI: https://doi.org/10.1007/s12035-017-0484-8

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