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Long Noncoding RNA FBXL19-AS1-Mediated Ulcerative Colitis-Associated Intestinal Epithelial Barrier Defect

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Tissue Engineering and Regenerative Medicine Aims and scope

Abstract

Background:

This study commenced to uncover the role of long non-coding RNA FBXL19 antisense RNA 1 (FBXL19-AS1) in the development of ulcerative colitis (UC) and its possible mechanism.

Methods:

FBXL19-AS1 expression in the colonic sigmoid mucosa of UC patients was detected. A colitis model was induced in mice using 5% dextran sodium sulfate. Hematoxylin–eosin staining was performed for histopathological examination. Apoptosis was detected by Tunel staining and tissue fibrosis was detected by immunohistochemistry. Also, intestinal permeability was examined. The concentrations of inflammatory factors IL-1β and IL-18 were detected by enzyme-linked immunosorbent assay. The relationship between FBXL19-AS1, miR-339-3p and RHOB was verified by RNA immunoprecipitation assay and dual luciferase reporter assay.

Results:

The expression of FBXL19-AS1 was increased in dextran sodium sulfate (DSS)-induced colitis mouse model. FBXL19-AS1 interference or miR-339-3p overexpression inhibited DSS-induced colonic epithelial cell apoptosis and inflammatory response, and improved intestinal epithelial barrier defects, thereby ameliorating DSS-induced colitis injury in mice. FBXL19-AS1 sponged miR-339-3p while miR-339-3p targeted RHOB. Overexpression of RHOB reversed the protective effect of inhibition of FBXL19-AS1 on DSS-induced colitis in mice.

Conclusion:

FBXL19-AS1 reduces miR-339-3p-mediated targeting of RHOB and aggravates intestinal epithelial barrier defect in DSS-induced colitis in mice.

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References

  1. Li Y, Li C, Tu Y, Tao J, Liu P, Xu H, et al. In vivo assessing colitis severity by topical administration of fluorescent probe against neutrophils. Talanta. 2021;233:122519.

    Article  CAS  PubMed  Google Scholar 

  2. Banskota S, Brim H, Kwon YH, Singh G, Sinha SR, Wang H, et al. Saffron pre-treatment promotes reduction in tissue inflammatory profiles and alters microbiome composition in experimental colitis mice. Molecules. 2021;26:3351.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Schmitz H, Barmeyer C, Fromm M, Runkel N, Foss HD, Bentzel CJ, et al. Altered tight junction structure contributes to the impaired epithelial barrier function in ulcerative colitis. Gastroenterology. 1999;116:301–9.

    Article  CAS  PubMed  Google Scholar 

  4. Sun C, Murata Y, Imada S, Konno T, Kotani T, Saito Y, et al. Role of Csk in intestinal epithelial barrier function and protection against colitis. Biochem Biophys Res Commun. 2018;504:109–14.

    Article  CAS  PubMed  Google Scholar 

  5. Turner JR. Intestinal mucosal barrier function in health and disease. Nat Rev Immunol. 2009;9:799–809.

    Article  CAS  PubMed  Google Scholar 

  6. Chen S, Liu H, Li Z, Tang J, Huang B, Zhi F, et al. Epithelial PBLD attenuates intestinal inflammatory response and improves intestinal barrier function by inhibiting NF-κB signaling. Cell Death Dis. 2021;12:563.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Lechuga S, Naydenov NG, Feygin A, Cruise M, Ervasti JM, Ivanov AI. Loss of β-cytoplasmic actin in the intestinal epithelium increases gut barrier permeability in vivo and exaggerates the severity of experimental colitis. Front Cell Dev Biol. 2020;8:588836.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Zhou J, Liu J, Gao Y, Shen L, Li S, Chen S. miRNA-based potential biomarkers and new molecular insights in ulcerative colitis. Front Pharmacol. 2021;12:707776.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Tang S, Guo W, Kang L, Liang J. MiRNA-182-5p aggravates experimental ulcerative colitis via sponging Claudin-2. J Mol Histol. 2021;52:1215–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Tian Y, Xu J, Li Y, Zhao R, Du S, Lv C, et al. MicroRNA-31 reduces inflammatory signaling and promotes regeneration in colon epithelium, and delivery of mimics in microspheres reduces colitis in mice. Gastroenterology. 2019;156:2281-96.e6.

    Article  CAS  PubMed  Google Scholar 

  11. Zhou C, Lu Y, Li X. miR-339-3p inhibits proliferation and metastasis of colorectal cancer. Oncol Lett. 2015;10:2842–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Jiang ZF, Zhang L. LncRNA: a potential research direction in intestinal barrier function. Dig Dis Sci. 2021;66:1400–8.

    Article  PubMed  Google Scholar 

  13. Xiong W, Yao M, Yang Y, Qu Y, Qian J. Implication of regulatory networks of long noncoding RNA/circular RNA-miRNA-mRNA in diabetic cardiovascular diseases. Epigenomics. 2020;12:1929–47.

    Article  CAS  PubMed  Google Scholar 

  14. Wang L, Zhang X, Liu Y, Xu S. Long noncoding RNA FBXL19-AS1 induces tumor growth and metastasis by sponging miR-203a-3p in lung adenocarcinoma. J Cell Physiol. 2020;235:3612–25.

    Article  CAS  PubMed  Google Scholar 

  15. Shen B, Yuan Y, Zhang Y, Yu S, Peng W, Huang X, et al. Long non-coding RNA FBXL19-AS1 plays oncogenic role in colorectal cancer by sponging miR-203. Biochem Biophys Res Commun. 2017;488:67–73.

    Article  CAS  PubMed  Google Scholar 

  16. Han J, Li Y, Zhang B, Liu H, Wu M, Zhang X. lncRNA TUG1 regulates ulcerative colitis through miR-142-5p/SOCS1 axis. Microb Pathog. 2020;143:104139.

    Article  CAS  PubMed  Google Scholar 

  17. Wang Y, Wang N, Cui L, Li Y, Cao Z, Wu X, et al. Long non-coding RNA MEG3 alleviated ulcerative colitis through upregulating miR-98-5p-sponged IL-10. Inflammation. 2021;44:1049–59.

    Article  CAS  PubMed  Google Scholar 

  18. Lv Q, Shi C, Qiao S, Cao N, Guan C, Dai Y, et al. Alpinetin exerts anti-colitis efficacy by activating AhR, regulating miR-302/DNMT-1/CREB signals, and therefore promoting Treg differentiation. Cell Death Dis. 2018;9:890.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Chen X, Xu T, Lv X, Zhang J, Liu S. Ginsenoside Rh2 alleviates ulcerative colitis by regulating the STAT3/miR-214 signaling pathway. J Ethnopharmacol. 2021;274:113997.

    Article  CAS  PubMed  Google Scholar 

  20. Lin S, Han Y, Jenkin K, Lee SJ, Sasaki M, Klapproth JM, et al. Lysophosphatidic acid receptor 1 is important for intestinal epithelial barrier function and susceptibility to colitis. Am J Pathol. 2018;188:353–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Jie F, Xiao S, Qiao Y, You Y, Feng Y, Long Y, et al. Kuijieling decoction suppresses NLRP3-Mediated pyroptosis to alleviate inflammation and experimental colitis in vivo and in vitro. J Ethnopharmacol. 2021;264:113243.

    Article  CAS  PubMed  Google Scholar 

  22. Luo Y, Xu H, Yang Z, Lin X, Zhao F, Huang Y, et al. Long non-coding RNA MALAT1 silencing elevates microRNA-26a-5p to ameliorate myocardial injury in sepsis by reducing regulator of calcineurin 2. Arch Biochem Biophys. 2022;715:109047.

    Article  CAS  PubMed  Google Scholar 

  23. Tian Y, Wang Y, Li F, Yang J, Xu Y, Ouyang M. LncRNA TUG1 regulates the balance of HuR and miR-29b-3p and inhibits intestinal epithelial cell apoptosis in a mouse model of ulcerative colitis. Hum Cell. 2021;34:37–48.

    Article  CAS  PubMed  Google Scholar 

  24. Rao J, Shao L, Lin M, Huang J, Fan L. LncRNA UCA1 accelerates the progression of ulcerative colitis via mediating the miR-331-3p/BRD4 axis. Int J Gen Med. 2021;14:2427–35.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Ye M, Wang C, Zhu J, Chen M, Wang S, Li M, et al. An NF-κB-responsive long noncoding RNA, PINT, regulates TNF-α gene transcription by scaffolding p65 and EZH2. FASEB J. 2021;35:e21667.

    Article  CAS  PubMed  Google Scholar 

  26. He D, Zhang X, Zhu X, Maharjan N, Wang Y, Luo P, et al. Identify and validate the transcriptomic, functional network, and predictive validity of FBXL19-AS1 in hepatocellular carcinoma. Front Oncol. 2020;10:609601.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Wan S, Ni G, Ding J, Huang Y. Long noncoding RNA FBXL19-AS1 expedites cell growth, migration and invasion in cervical cancer by miR-193a-5p/PIN1 signaling. Cancer Manag Res. 2020;12:9741–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Pan R, He Z, Ruan W, Li S, Chen H, Chen Z, et al. lncRNA FBXL19-AS1 regulates osteosarcoma cell proliferation, migration and invasion by sponging miR-346. Onco Targets Ther. 2018;11:8409–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Dong G, Pan T, Zhou D, Li C, Liu J, Zhang J. FBXL19-AS1 promotes cell proliferation and inhibits cell apoptosis via miR-876-5p/FOXM1 axis in breast cancer. Acta Biochim Biophys Sin (Shanghai). 2019;51:1106–13.

    Article  CAS  Google Scholar 

  30. Ma Q, Gan GF, Niu Y, Tong SJ. Analysis of associations of FBXL19-AS1 with occurrence, development and prognosis of acute pancreatitis. Eur Rev Med Pharmacol Sci. 2020;24:12763–9.

    CAS  PubMed  Google Scholar 

  31. Liu X, Wu P, Su R, Xue Y, Yang C, Wang D, et al. IGF2BP2 stabilized FBXL19-AS1 regulates the blood-tumour barrier permeability by negatively regulating ZNF765 by STAU1-mediated mRNA decay. RNA Biol. 2020;17:1777–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Odenwald MA, Turner JR. The intestinal epithelial barrier: a therapeutic target? Nat Rev Gastroenterol Hepatol. 2017;14:9–21.

    Article  CAS  PubMed  Google Scholar 

  33. McGilligan VE, Wallace JM, Heavey PM, Ridley DL, Rowland IR. The effect of nicotine in vitro on the integrity of tight junctions in Caco-2 cell monolayers. Food Chem Toxicol. 2007;45:1593–8.

    Article  CAS  PubMed  Google Scholar 

  34. Sacco A, Bruno A, Contursi A, Dovizio M, Tacconelli S, Ricciotti E, et al. Platelet-specific deletion of cyclooxygenase-1 ameliorates dextran sulfate sodium-induced colitis in mice. J Pharmacol Exp Ther. 2019;370:416–26.

    Article  CAS  PubMed  Google Scholar 

  35. Jia Q, Zhang H, Su Y, Liu X, Bai J, Lang W, et al. Strictosamide alleviates the inflammation in an acute ulcerative colitis (UC) model. J Physiol Biochem. 2021;77:283–94.

    Article  CAS  PubMed  Google Scholar 

  36. Qiao C, Yang L, Wan J, Liu X, Pang C, You W, et al. Long noncoding RNA ANRIL contributes to the development of ulcerative colitis by miR-323b-5p/TLR4/MyD88/NF-κB pathway. Biochem Biophys Res Commun. 2019;508:217–24.

    Article  CAS  PubMed  Google Scholar 

  37. Trakunram K, Chaniad P, Geater SL, Keeratichananont W, Chittithavorn V, Uttayamakul S, et al. Serum miR-339-3p as a potential diagnostic marker for non-small cell lung cancer. Cancer Biol Med. 2020;17:652–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Wang S, Su TT, Tong H, Shi W, Ma F, Quan Z. CircPVT1 promotes gallbladder cancer growth by sponging miR-339-3p and regulates MCL-1 expression. Cell Death Discov. 2021;7:191.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Liu Y, Zhang W, Wang S, Cai L, Jiang Y, Pan Y, et al. Cullin3-TNFAIP1 E3 ligase controls inflammatory response in hepatocellular carcinoma cells via ubiquitination of RhoB. Front Cell Dev Biol. 2021;9:617134.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Khan A, Ni W, Lopez-Giraldez F, Kluger MS, Pober JS, Pierce RW. Tumor necrosis factor-induced ArhGEF10 selectively activates RhoB contributing to human microvascular endothelial cell tight junction disruption. FASEB J. 2021;35:e21627.

    Article  CAS  PubMed  Google Scholar 

  41. Privat M, Cavard A, Zekri Y, Ponelle-Chachuat F, Molnar I, Sonnier N, et al. A high expression ratio of RhoA/RhoB is associated with the migratory and invasive properties of basal-like breast tumors. Int J Med Sci. 2020;17:2799–808.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Yang Y, Ma Y, Shi C, Chen H, Zhang H, Chen N, et al. Overexpression of miR-21 in patients with ulcerative colitis impairs intestinal epithelial barrier function through targeting the Rho GTPase RhoB. Biochem Biophys Res Commun. 2013;434:746–52.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

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Funding

This work was financially supported by Cultivation Fund of National Natural Science Foundation (Grant No. qiankehe2018-5764–11).

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Correspondence to Xun Zhao.

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Ethical statement

he experiment research protocol was approved by the Ethics Committee of Guizhou Provincial People’s Hospital and all experimental procedures conformed with institutional guidelines, and all patients participating in this study provided written informed consent in accordance with the “Helsinki Declaration”, Animal care were approved by Guizhou Provincial People’s Hospital Animal Care Committee and performed according to NIH guidelines (Approval NO. GZ201609BP601).

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13770_2022_479_MOESM1_ESM.tif

Supplementary Fig. 1 Gene expression analysisA. FBXL19-AS1 expression in mouse colon tissue; B. miR-339-3p expression in mouse colon tissue; C. RHOB expression in colon tissue of mice. (TIF 4386 KB)

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Zhao, X., Cui, DJ., Yang, Lc. et al. Long Noncoding RNA FBXL19-AS1-Mediated Ulcerative Colitis-Associated Intestinal Epithelial Barrier Defect. Tissue Eng Regen Med 19, 1077–1088 (2022). https://doi.org/10.1007/s13770-022-00479-9

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