Skip to main content

Advertisement

SpringerLink
Log in

RETRACTED ARTICLE: Knockdown of long non-coding RNA TUG1 depresses apoptosis of hippocampal neurons in Alzheimer’s disease by elevating microRNA-15a and repressing ROCK1 expression

  • Original Research Article
  • Published:
Inflammation Research Aims and scope Submit manuscript

This article was retracted on 05 September 2022

This article has been updated

Abstract

Objective

Many studies have already suggested the role of long non-coding RNAs (lncRNAs) in Alzheimer’s disease (AD), but the functions of lncRNA Taurine Upregulated Gene 1 (TUG1) in AD have been scarcely discussed. This study aims to verify how TUG1 affects hippocampal neurons in AD through modulation of microRNA-15a (miR-15a)/Rho-associated protein kinase 1 (ROCK1).

Method

AD mice was modeled through injection of β-amyloid 25-35 (Aβ25-35) into the lateral ventricle. After modeling, the mice were injected with altered TUG1 and/or miR-15a agomir lentiviruses. The spatial learning ability and memory ability of mice were detected through Morris water maze test. Hippocampal neuronal apoptosis and oxidative stress indicators in AD mice were then detected. The hippocampal neuron AD model was induced by Aβ25-35. Next, the neurons were, respectively, transfected with altered TUG1 vector and/or miR-15a mimics to determine the proliferation inhibition and apoptosis of hippocampal neurons. The interactions between TUG1 and miR-15a, and between miR-15a and ROCK1 were assessed using bioinformatic prediction, dual luciferase reporter gene assay and RNA-pull-down assay.

Results

In the animal models, Aβ25-35-induced mice exhibited decreased spatial learning and memory ability, obvious pathological injury, promoted hippocampal neuronal apoptosis and decreased antioxidant ability. TUG1 silencing and miR-15a elevation improved spatial learning ability and memory ability, ameliorated pathological injury, depressed neuronal apoptosis, and strengthened antioxidant ability of hippocampal neurons in AD mice. In cellular models, Aβ25-35-treated hippocampal neurons presented inhibited neuronal viability and promoted neuronal apoptosis. TUG1 silencing and miR-15a elevation increased viability and limited apoptosis of Aβ25-35-treated hippocampal neurons. TUG1 specifically bound to miR-15a, and miR-15a targeted ROCK1.

Conclusion

Collectively, this study reveals that TUG1 knockdown restricts apoptosis of hippocampal neurons in AD by elevating miR-15a and suppressing ROCK1 expression, and provides a new therapeutic target for AD treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Change history

References

  1. Alzheimer’s A. 2016 Alzheimer’s disease facts and figures. Alzheimers Dement. 2016;12(4):459–509.

    Article  Google Scholar 

  2. Ballard C, et al. Alzheimer’s disease. Lancet. 2011;377(9770):1019–31.

    Article  Google Scholar 

  3. Lane CA, Hardy J, Schott JM. Alzheimer’s disease. Eur J Neurol. 2018;25(1):59–70.

    Article  CAS  Google Scholar 

  4. Hodson R. Alzheimer’s disease. Nature. 2018;559(7715):S1.

    Article  CAS  Google Scholar 

  5. Riva P, Ratti A, Venturin M. The long non-coding RNAs in neurodegenerative diseases: novel mechanisms of pathogenesis. Curr Alzheimer Res. 2016;13(11):1219–31.

    Article  CAS  Google Scholar 

  6. Cortini F, Roma F, Villa C. Emerging roles of long non-coding RNAs in the pathogenesis of Alzheimer’s disease. Ageing Res Rev. 2019;50:19–26.

    Article  CAS  Google Scholar 

  7. Yue D, et al. Silencing of long noncoding RNA XIST attenuated Alzheimer’s disease-related BACE1 alteration through miR-124. Cell Biol Int. 2020;44(2):630–6.

    Article  Google Scholar 

  8. Fotuhi SN, et al. Long non-coding RNA BACE1-AS may serve as an Alzheimer’s disease blood-based biomarker. J Mol Neurosci. 2019;69(3):351–9.

    Article  CAS  Google Scholar 

  9. Wang H, Lu B, Chen J. Knockdown of lncRNA SNHG1 attenuated Abeta25-35-inudced neuronal injury via regulating KREMEN1 by acting as a ceRNA of miR-137 in neuronal cells. Biochem Biophys Res Commun. 2019;518(3):438–44.

    Article  CAS  Google Scholar 

  10. Yu C, et al. LncRNA TUG1 sponges miR-204-5p to promote osteoblast differentiation through upregulating Runx2 in aortic valve calcification. Cardiovasc Res. 2018;114(1):168–79.

    Article  CAS  Google Scholar 

  11. Chen S, et al. LncRNA TUG1 sponges microRNA-9 to promote neurons apoptosis by up-regulated Bcl2l11 under ischemia. Biochem Biophys Res Commun. 2017;485(1):167–73.

    Article  Google Scholar 

  12. Cao C, et al. Small interfering LncRNA-TUG1 (siTUG1) decreases ketamine-induced neurotoxicity in rat hippocampal neurons. Int J Neurosci. 2019;129(10):937–44.

    Article  Google Scholar 

  13. Braga TV, et al. Evaluation of MiR-15a and MiR-16-1 as prognostic biomarkers in chronic lymphocytic leukemia. Biomed Pharmacother. 2017;92:864–9.

    Article  CAS  Google Scholar 

  14. Wang J, et al. Genome-wide circulating microRNA expression profiling indicates biomarkers for epilepsy. Sci Rep. 2015;5:9522.

    Article  Google Scholar 

  15. Yang S, et al. Dietary advanced glycation end products-induced cognitive impairment in aged ICR mice: protective role of quercetin. Mol Nutr Food Res. 2020;64(3):e1901019.

    Article  Google Scholar 

  16. Hebert SS, et al. Genetic ablation of Dicer in adult forebrain neurons results in abnormal tau hyperphosphorylation and neurodegeneration. Hum Mol Genet. 2010;19(20):3959–69.

    Article  CAS  Google Scholar 

  17. Qin Z, et al. MiR-199a targeting ROCK1 to affect kidney cell proliferation, invasion and apoptosis. Artif Cells Nanomed Biotechnol. 2018;46(8):1920–5.

    CAS  PubMed  Google Scholar 

  18. Hu YB, et al. ROCK1 is associated with Alzheimer’s disease-specific plaques, as well as enhances autophagosome formation but not autophagic abeta clearance. Front Cell Neurosci. 2016;10:253.

    PubMed  PubMed Central  Google Scholar 

  19. Henderson BW, et al. Rho-associated protein kinase 1 (ROCK1) is increased in Alzheimer’s disease and ROCK1 depletion reduces amyloid-beta levels in brain. J Neurochem. 2016;138(4):525–31.

    Article  CAS  Google Scholar 

  20. Weller J, Budson A. Current understanding of Alzheimer’s disease diagnosis and treatment. F1000Research. 2018;7.

  21. Briggs R, Kennelly SP, O’Neill D. Drug treatments in Alzheimer’s disease. Clin Med (Lond). 2016;16(3):247–53.

    Article  Google Scholar 

  22. Zhang Z. Long non-coding RNAs in Alzheimer’s disease. Curr Top Med Chem. 2016;16(5):511–9.

    Article  CAS  Google Scholar 

  23. Yun-Bo F, et al. LncRNA TUG1 is upregulated and promotes cell proliferation in osteosarcoma. Open Med (Wars). 2016;11(1):163–7.

    Article  Google Scholar 

  24. Zhao L, et al. The Lncrna-TUG1/EZH2 axis promotes pancreatic cancer cell proliferation, migration and EMT phenotype formation through sponging Mir-382. Cell Physiol Biochem. 2017;42(6):2145–58.

    Article  CAS  Google Scholar 

  25. Liu B, et al. MiR-15a suppresses hepatocarcinoma cell migration and invasion by directly targeting cMyb. Am J Transl Res. 2017;9(2):520–32.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Wang ZM, et al. miR-15a-5p suppresses endometrial cancer cell growth via Wnt/beta-catenin signaling pathway by inhibiting WNT3A. Eur Rev Med Pharmacol Sci. 2017;21(21):4810–8.

    PubMed  Google Scholar 

  27. Luo D, et al. Activation of the ROCK1/MMP-9 pathway is associated with the invasion and poor prognosis in papillary thyroid carcinoma. Int J Oncol. 2017;51(4):1209–18.

    Article  CAS  Google Scholar 

  28. Wang Y, et al. MicroRNA-335 and its target Rock1 synergistically influence tumor progression and prognosis in osteosarcoma. Oncol Lett. 2017;13(5):3057–65.

    Article  CAS  Google Scholar 

  29. Cao J, et al. TUG1 promotes osteosarcoma tumorigenesis by upregulating EZH2 expression via miR-144-3p. Int J Oncol. 2017;51(4):1115–23.

    Article  CAS  Google Scholar 

  30. Wang G, et al. MicroRNA-146a suppresses ROCK1 allowing hyperphosphorylation of tau in Alzheimer’s disease. Sci Rep. 2016;6:26697.

    Article  CAS  Google Scholar 

  31. Hu Y, et al. Upregulation of long noncoding RNA TUG1 promotes cervical cancer cell proliferation and migration. Cancer Med. 2017;6(2):471–82.

    Article  CAS  Google Scholar 

  32. Zhu J, et al. Long non-coding RNA TUG1 promotes cervical cancer progression by regulating the miR-138-5p-SIRT1 axis. Oncotarget. 2017;8(39):65253–64.

    Article  Google Scholar 

  33. Han X, et al. LncRNA TUG1 affects cell viability by regulating glycolysis in osteosarcoma cells. Gene. 2018;674:87–92.

    Article  CAS  Google Scholar 

  34. Zhang B, et al. MiR-16 regulates cell death in Alzheimer’s disease by targeting amyloid precursor protein. Eur Rev Med Pharmacol Sci. 2015;19(21):4020–7.

    CAS  PubMed  Google Scholar 

  35. Zhang Y, et al. MiR-214-3p attenuates cognition defects via the inhibition of autophagy in SAMP8 mouse model of sporadic Alzheimer’s disease. Neurotoxicology. 2016;56:139–49.

    Article  CAS  Google Scholar 

  36. Qin SB, et al. MiR-182-5p inhibited oxidative stress and apoptosis triggered by oxidized low-density lipoprotein via targeting toll-like receptor 4. J Cell Physiol. 2018;233(10):6630–7.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We would like to acknowledge the reviewers for their helpful comments on this paper.

Funding

None.

Author information

Authors and Affiliations

  1. Department of Rehabilitation Medicine, Weihai Central Hospital, No. 3, East Mishan Road, Wendeng District, Weihai, 264400, Shandong, China

    Xia Li, Xi-Ling LI, Feng-Yuan Yu & Hai-Ming Cong

  2. Department of Neurology, Weihai Central Hospital, Weihai, 264400, Shandong, China

    Sheng-Wu Wang

Authors
  1. Xia Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sheng-Wu Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xi-Ling LI
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Feng-Yuan Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hai-Ming Cong
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

HC finished study design, XL, SW finished experimental studies, XL, XLL, FY finished data analysis, XL finished manuscript editing. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Hai-Ming Cong.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical statement

This study was approved and supervised by the animal ethics committee of Weihai Central Hospital (ethical number: 201800413). The treatment of animals in all experiments conforms to the ethical standards of experimental animals.

Additional information

Responsible Editor: John Di Battista.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article has been retracted. Please see the retraction notice for more detail:https://doi.org/10.1007/s00011-022-01631-w

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, X., Wang, SW., LI, XL. et al. RETRACTED ARTICLE: Knockdown of long non-coding RNA TUG1 depresses apoptosis of hippocampal neurons in Alzheimer’s disease by elevating microRNA-15a and repressing ROCK1 expression. Inflamm. Res. 69, 897–910 (2020). https://doi.org/10.1007/s00011-020-01364-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00011-020-01364-8

Keywords

Search

Navigation