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Long Non-coding RNA MEG3 Alleviated Ulcerative Colitis Through Upregulating miR-98-5p-Sponged IL-10

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Abstract

Ulcerative colitis (UC) is a refractory chronic colitis disease with the particularly complex cause. Recently, long noncoding RNAs (lncRNAs) have been reported to be related to the development of UC. LncRNA MEG3 has been proved to play an anti-inflammatory role in a variety of inflammatory diseases, which share similar pathogenesis with UC, indicating the potential involvement of lncRNA MEG3 in UC. This study aims to investigate the functional role and underlying mechanism of lncRNA MEG3 in UC. Gradient concentration of H2O2 (0, 20, 50, 100, and 200 μM) was used to induce Caco-2 damage models in vitro. Cell viability was detected by cell counting kit-8 (CCK-8) assay. LncRNA MEG3, miR-98-5p, and IL-10 levels in H2O2−treated Caco-2 cells were assessed by performing real-time quantitative polymerase chain reaction (RT-qPCR). Moreover, the binding relationship between lncRNA MEG3 and miR-98-5p, as well as the binding relationship between miR-98-5p and IL-10, was validated using dual-luciferase reporter assay. 2, 4, 6-Trinitrobenzenesulfonic acid solution (TNBS) was applied to induce ulcerative colitis in young rats. The body weight, disease activity index (DAI), length and weight of the colons, pathological scores of UC rats, reactive oxygen species (ROS), and inflammatory cytokines were determined to evaluate the effects of lncRNA MEG3 on the progression of UC. Besides, hematoxylin-eosin (HE) staining was exploited to observe histological changes of UC rat colons. In addition, western blotting analysis was also performed to evaluate the apoptosis and pyroptosis-related protein levels. Moreover, lncRNA MEG3, miR-98-5p, and IL-10 levels in UC rat colons were further assessed by RT-qPCR. Meanwhile, IL-10 expression was determined using immunohistochemistry. LncRNA MEG3 and IL-10 levels were distinctly decreased while miR-98-5p was increased in Caco-2 damage models and UC rats. Bioinformatics analysis predicted the binding sites of lncRNA MEG3 to miR-98-5p and miR-98-5p to IL-10. Besides, dual-luciferase reporter assay validated the negative correlation between lncRNA MEG3 and miR-98-5p, miR-98-5p, and IL-10. Overexpressed lncRNA MEG3 reduced. DAI scores and colon weight/length ratio improved UC ulceration. In addition, upregulation of lncRNA MEG3 relieved oxidative stress, inflammatory response, apoptosis, and pyroptosis of UC rat colons. LncRNA MEG3 overexpression alleviates the serve ulceration of UC rat colons by upregulating IL-10 expression via sponging miR-98-5p. To sum up, this study reveals the protective role of lncRNA MEG3 in the development of UC and may provide potential therapeutic targets for UC.

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Data Availability

Data sets during the current study are available from the corresponding author on reasonable request.

References

  1. Gajendran, M., P. Loganathan, G. Jimenez, A.P. Catinella, N. Ng, C. Umapathy, N. Ziade, and J.G. Hashash. 2019. A comprehensive review and update on ulcerative colitis. Disease-a-month: DM 65: 100851.

    Article  Google Scholar 

  2. Gravina, A.G., M. Dallio, M. Masarone, V. Rosato, A. Aglitti, M. Persico, C. Loguercio, and A. Federico. 2018. Vascular endothelial dysfunction in inflammatory bowel diseases: pharmacological and nonpharmacological targets. Oxidative Medicine and Cellular Longevity 2018: 2568569.

    Article  Google Scholar 

  3. John, E.S., K. Katz, M. Saxena, S. Chokhavatia, and S. Katz. 2016. Management of Inflammatory Bowel Disease in the elderly. Current Treatment Options in Gastroenterology 14: 285–304.

    Article  Google Scholar 

  4. Shivaji, U.N., O.M. Nardone, R. Cannatelli, S.C. Smith, S. Ghosh, and M. Iacucci. 2020. Small molecule oral targeted therapies in ulcerative colitis. The Lancet. Gastroenterology & Hepatology 5: 850–861.

    Article  Google Scholar 

  5. Ahluwalia, B., L. Moraes, M.K. Magnusson, and L. Öhman. 2018. Immunopathogenesis of inflammatory bowel disease and mechanisms of biological therapies. Scandinavian Journal of Gastroenterology 53: 379–389.

    Article  Google Scholar 

  6. Hanić, M., I. Trbojević-Akmačić, and G. Lauc. 2019. Inflammatory bowel disease - glycomics perspective. Biochimica et Biophysica Acta, General Subjects 1863: 1595–1601.

    Article  Google Scholar 

  7. Saber, S., R.M. Khalil, W.S. Abdo, D. Nassif, and E. El-Ahwany. 2019. Olmesartan ameliorates chemically-induced ulcerative colitis in rats via modulating NFκB and Nrf-2/HO-1 signaling crosstalk. Toxicology and Applied Pharmacology 364: 120–132.

    Article  CAS  Google Scholar 

  8. Chao, L., Z. Li, J. Zhou, W. Chen, Y. Li, W. Lv, A. Guo, Q. Qu, and S. Guo. 2020. Shen-Ling-Bai-Zhu-San improves dextran sodium sulfate-induced colitis by inhibiting caspase-1/caspase-11-mediated pyroptosis. Frontiers in Pharmacology 11: 814.

    Article  CAS  Google Scholar 

  9. McKenzie, B.A., V.M. Dixit, and C. Power. 2020. Fiery cell death: pyroptosis in the central nervous system. Trends in Neurosciences 43: 55–73.

    Article  CAS  Google Scholar 

  10. Paul, G., V. Khare, and C. Gasche. 2012. Inflamed gut mucosa: Downstream of interleukin-10. European Journal of Clinical Investigation 42: 95–109.

    Article  CAS  Google Scholar 

  11. Fang, D., and J. Zhu. 2020. Molecular switches for regulating the differentiation of inflammatory and IL-10-producing anti-inflammatory T-helper cells. Cellular and Molecular Life Sciences: CMLS 77: 289–303.

    Article  CAS  Google Scholar 

  12. Ghizoni, J.S., R. Nichele, M.T. de Oliveira, S. Pamato, and J.R. Pereira. 2020. The utilization of saliva as an early diagnostic tool for oral cancer: microRNA as a biomarker. Clinical & Translational Oncology: Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 22: 804–812.

    Article  CAS  Google Scholar 

  13. Soroosh, A., M. Koutsioumpa, C. Pothoulakis, and D. Iliopoulos. 2018. Functional role and therapeutic targeting of microRNAs in inflammatory bowel disease. American Journal of Physiology. Gastrointestinal and Liver Physiology 314: G256–256G262.

    Article  Google Scholar 

  14. Naghdalipour, M., N. Moradi, R. Fadaei, S. Rezghi Barez, S. Sayyahfar, M. Mokhtare, T.K. Fard, S. Fallah, and A. Esteghamati. 2020. Alteration of miR-21, miR-433 and miR-590 tissue expression related to the TGF-β signaling pathway in ulcerative colitis patients. Archives of Physiology and Biochemistry 15: 1–5.

    Article  Google Scholar 

  15. Peng, Y., Q. Wang, W. Yang, Q. Yang, Y. Pei, and W. Zhang. 2020. MiR-98-5p expression inhibits polarization of macrophages to an M2 phenotype by targeting Trib1 in inflammatory bowel disease. Acta Biochimica Polonica 67: 157–163.

    CAS  PubMed  Google Scholar 

  16. Takuse, Y., M. Watanabe, N. Inoue, R. Ozaki, H. Ohtsu, M. Saeki, Y. Katsumata, Y. Hidaka, and Y. Iwatani. 2017. Association of IL-10-regulating MicroRNAs in peripheral blood mononuclear cells with the pathogenesis of autoimmune thyroid disease. Immunological Investigations 46: 590–602.

    Article  CAS  Google Scholar 

  17. Gabriel, A.F., M.C. Costa, and F.J. Enguita. 2020. Interactions among regulatory non-coding RNAs involved in cardiovascular diseases. Advances in Experimental Medicine and Biology 1229: 79–104.

    Article  CAS  Google Scholar 

  18. Shaker, O.G., M.A. Ali, T.I. Ahmed, O.M. Zaki, D.Y. Ali, E.A. Hassan, N.F. Hemeda, and M.N. AbdelHafez. 2019. Association between LINC00657 and miR-106a serum expression levels and susceptibility to colorectal cancer, adenomatous polyposis, and ulcerative colitis in Egyptian population. IUBMB Life 71: 1322–1335.

    Article  CAS  Google Scholar 

  19. Qiao, C., L. Yang, J. Wan, X. Liu, C. Pang, W. You, and G. Zhao. 2019. Long noncoding RNA ANRIL contributes to the development of ulcerative colitis by miR-323b-5p/TLR4/MyD88/NF-κB pathway. Biochemical and Biophysical Research Communications 508: 217–224.

    Article  CAS  Google Scholar 

  20. Li, Y., S. Zhang, C. Zhang, and M. Wang. 2020. LncRNA MEG3 inhibits the inflammatory response of ankylosing spondylitis by targeting miR-146a. Molecular and Cellular Biochemistry 466: 17–24.

    Article  CAS  Google Scholar 

  21. Li, G., Y. Liu, F. Meng, Z. Xia, X. Wu, Y. Fang, C. Zhang, Y. Zhang, and D. Liu. 2019. LncRNA MEG3 inhibits rheumatoid arthritis through miR-141 and inactivation of AKT/mTOR signalling pathway. Journal of Cellular and Molecular Medicine 23: 7116–7120.

    Article  CAS  Google Scholar 

  22. Xu, B., Y.L. Li, M. Xu, C.C. Yu, M.Q. Lian, Z.Y. Tang, C.X. Li, and Y. Lin. 2017. Geniposide ameliorates TNBS-induced experimental colitis in rats via reducing inflammatory cytokine release and restoring impaired intestinal barrier function. Acta Pharmacologica Sinica 38: 688–698.

    Article  CAS  Google Scholar 

  23. Livak, K.J., and T.D. Schmittgen. 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods: a Companion to Methods in Enzymology 25: 402–408.

    Article  CAS  Google Scholar 

  24. Zhao, K., J.Y. Tan, Q.D. Mao, K.Y. Ren, B.G. He, C.P. Zhang, and L.Z. Wei. 2019. Overexpression of long non-coding RNA TUG1 alleviates TNF-α-induced inflammatory injury in interstitial cells of Cajal. European Review for Medical and Pharmacological Sciences 23: 312–320.

    CAS  PubMed  Google Scholar 

  25. De Trez, C., B. Stijlemans, V. Bockstal, J. Cnops, H. Korf, J. Van Snick, G. Caljon, E. Muraille, I.R. Humphreys, L. Boon, J.A. Van Ginderachter, and S. Magez. 2020. A critical blimp-1-dependent IL-10 regulatory pathway in T cells protects from a lethal pro-inflammatory cytokine storm during acute experimental Trypanosoma brucei infection. Frontiers in Immunology 11: 1085.

    Article  Google Scholar 

  26. Wang, Q., J. Wu, Y. Zeng, K. Chen, C. Wang, S. Yang, N. Sun, H. Chen, K. Duan, and G. Zeng. 2020. Pyroptosis: A pro-inflammatory type of cell death in cardiovascular disease. Clinica Chimica Acta; International Journal of Clinical Chemistry 510: 6272.

    Article  CAS  Google Scholar 

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Authors and Affiliations

Authors

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Yan Wang, Nan Wang, Lianlian Cui, Yan Li, and Yanbo Cheng searched the literature and designed the study. All the authors performed the experiments, analyzed the data, and wrote the manuscript. Yan Wang and Yanbo Cheng revised the manuscript.

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Correspondence to Yanbo Cheng.

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All experimental procedures were approved by the Animal Ethics Committee of Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, People’ s Hospital of Henan University.

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Wang, Y., Wang, N., Cui, L. et al. Long Non-coding RNA MEG3 Alleviated Ulcerative Colitis Through Upregulating miR-98-5p-Sponged IL-10. Inflammation 44, 1049–1059 (2021). https://doi.org/10.1007/s10753-020-01400-z

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  • DOI: https://doi.org/10.1007/s10753-020-01400-z

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