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GAB1, KCNQ1OT1, migration, miR-183-3p, proliferation, psoriasis
Background: Differentially expressed long non-coding RNAs (lncRNA) have been reported to be involved in the proliferation and migration of keratinocyte. Potassium voltage-gated channel subfamily Q member 1 overlapping transcript 1 (KCNQ1OT1) was implicated in the pathogenesis of various diseases, including cancer, sepsis, diabetic cardiomyopathy, and atherosclerosis. In this study, the influence of KCNQ1OT1 on the proliferation and migration of psoriatic keratinocytes was explained.
Methods: Cultured human keratinocyte cell line (HaCaT) was incubated with tumor necrosis factor-α (TNF-α). Cell viability and migration were assessed by MTT assay and wound healing, respectively. Target miRNA of KCNQ1OT1 was identified by luciferase activity and RNA immunoprecipitation (RIP) assays.
Results: KCNQ1OT1 was up-regulated in TNF-α-treated HaCaT cell line, and knockdown of KCNQ1OT1 reduced viability and suppressed the migration of TNF-α-treated HaCaT cell line. KCNQ1OT1 was bound to microRNA-183-3p (miR-183-3p) and negatively regulated its expression. Over-expression of growth factor receptor binding 2-associated binding protein 1 (GAB1) counteracted with the suppressive effects of KCNQ1OT1-induced silence on the viability and migration of TNF-α-treated HaCaT cells.
Conclusion: KCNQ1OT1 silence suppressed the proliferation and migration of TNF-α-treated HaCaT cells through regulation of miR-183-3p/GAB1.
2. Kim J, Krueger JG. The immunopathogenesis of psoriasis. Dermatol Clin. 2015;33(1):13–23. https://doi.org/10.1016/j.det.2014.09.002
3. Zhang Y, Tu C, Zhang D, Zheng Y, Peng Z, Feng Y, et al. Wnt/β-catenin and Wnt5a/Ca pathways regulate proliferation and apoptosis of keratinocytes in psoriasis lesions. Cell Physiol Biochem. 2015;36:1890–902. https://doi.org/10.1159/000430158
4. Lulevich V, Yang H-y, Rivkah Isseroff R, Liu G-y. Single cell mechanics of keratinocyte cells. Ultramicroscopy. 2010;110(12):1435–42. https://doi.org/10.1016/j.ultramic.2010.07.009
5. Hawkes JE, Chan TC, Krueger JG. Psoriasis pathogenesis and the development of novel targeted immune therapies. J Allergy Clin Immunol. 2017;140(3):645–53. https://doi.org/10.1016/j.jaci.2017.07.004
6. Zhang W, Yi X, An Y, Guo S, Li S, Song P, et al. MicroRNA-17-92 cluster promotes the proliferation and the chemokine production of keratinocytes: Implication for the pathogenesis of psoriasis. Cell Death Dis. 2018;9(5):567–567. https://doi.org/10.1038/s41419-018-0621-y
7. Gupta R, Ahn R, Lai K, Mullins E, Debbaneh M, Dimon M, et al. Landscape of long noncoding RNAs in psoriatic and healthy skin. J Invest Dermatol. 2016;136(3):603–9. https://doi.org/10.1016/j.jid.2015.12.009
8. Song J-K, Yin S-Y, Li W, Li X-D, Luo Y, Luo Y, et al. An update on the role of long non-coding RNAs in psoriasis. Chinese Med J. 2021;134(4):379-383. https://doi.org/10.1097/CM9.0000000000001243
9. Li D, Kular L, Vij M, Herter EK, Li X, Wang A, et al. Human skin long noncoding RNA WAKMAR1 regulates wound healing by enhancing keratinocyte migration. Proc Nat Acad Sci. 2019;116(19):9443–52. https://doi.org/10.1073/pnas.1814097116
10. Jia H-Y, Zhang K, Lu W-J, Xu G-W, Zhang J-F, Tang Z-L. LncRNA MEG3 influences the proliferation and apoptosis of psoriasis epidermal cells by targeting miR-21/caspase-8. BMC Mol Cell Biol. 2019;20(1):46–46. https://doi.org/10.1186/s12860-019-0229-9
11. Yao Y, Wang X, Gao J. LncRNA KCNQ1OT1 sponges miR-206 to ameliorate neural injury induced by anesthesia via up-regulating BDNF. Drug Des Devel Ther. 2020;14:4789–800. https://doi.org/10.2147/DDDT.S256319
12. Gao X, Ge J, Li W, Zhou W, Xu L. LncRNA KCNQ1OT1 promotes osteogenic differentiation to relieve osteolysis via Wnt/β-catenin activation. Cell Biosci. 2018;8(1):19. https://doi.org/10.1186/s13578-018-0216-4
13. Lin Z-B, Long P, Zhao Z, Zhang Y-R, Chu X-D, Zhao X-X, et al. Long noncoding RNA KCNQ1OT1 is a prognostic biomarker and mediates CD8<sup>+</sup> T cell exhaustion by regulating CD155 expression in colorectal cancer [Internet]. Int J Biol Sci. 2021;17(7):1757–68. Available from: http://europepmc.org/abstract/MED/33994860
https://doi.org/10.7150/ijbs.59001; https://europepmc.org/articles/PMC8120463; https://europepmc.org/articles/PMC8120463?pdf=render
14. Zhu Y, Shen Y, Chen R, Li H, Wu Y, Zhang F, et al. KCNQ1OT1 lncRNA affects the proliferation, apoptosis, and chemoresistance of small cell lung cancer cells via the JAK2/STAT3 axis. Ann Transl Med. 2021;9(10):891-891. https://doi.org/10.21037/atm-21-1761
15. Shen Y, Xu J, Pan X, Zhang Y, Weng Y, Zhou D, et al. LncRNA KCNQ1OT1 sponges miR-34c-5p to promote osteosarcoma growth via ALDOA enhanced aerobic glycolysis. Cell Death Dis. 2020;11(4):278-278. https://doi.org/10.1038/s41419-020-2485-1
16. Jiang X, Yu M, Zhu T, Lou L, Chen X, Li Q, et al. Kcnq1ot1/miR-381-3p/ETS2 axis regulates inflammation in mouse models of acute respiratory distress syndrome. Mol Ther Nucleic Acids. 2020;19:179–89. https://doi.org/10.1016/j.omtn.2019.10.036
17. Chen L, Xiong Y, Yan C, Zhou W, Endo Y, Xue H, et al. LncRNA KCNQ1OT1 accelerates fracture healing via modulating miR-701-3p/FGFR3 axis. FASEB J. 2020;34(4):5208–22. https://doi.org/10.1096/fj.201901864RR*******
18. Huang Y. The novel regulatory role of lncRNA-miRNA-mRNA axis in cardiovascular diseases. J Cell Mol Med. 2018;22(12):5768–75. https://doi.org/10.1111/jcmm.13866
19. Li J, Tong Y, Zhou Y, Han Z, Wang X, Ding T, et al. LncRNA KCNQ1OT1 as a miR-26a-5p sponge regulates ATG12-mediated cardiomyocyte autophagy and aggravates myocardial infarction. Intern J Cardiol.2021;388:14-23 https://doi.org/ 10.1016/j.ijcard.2021.05.053
20. Ling C, Hu X, Luo L, Liang C, Wang H, Chen C. Phoenixin-14 regulates proliferation and apoptosis of vascular smooth muscle cells by modulation of KCNQ1OT1/miR-183-3p/CTNNB1 axis. Environ Toxicol Pharmacol. 2021;86:103655. https://doi.org/10.1016/j.etap.2021.103655
21. Liu T, Zhang X, Wang Y. miR-183-3p suppresses proliferation and migration of keratinocyte in psoriasis by inhibiting GAB1. Hereditas. 2020;157(1):28-28. https://doi.org/10.1186/s41065-019-0104-x; https://doi.org/10.1186/s41065-020-00138-w
22. Choi DH, Hwang HS. Anti-inflammation activity of Brazilin in TNF-α induced human psoriasis dermatitis skin model. Appl Biol Chem. 2019;62(1):46. https://doi.org/10.1186/s13765-019-0455-z
23. Rendon A, Schäkel K. Psoriasis pathogenesis and treatment. Int J Mol Sci. 2019;20(6):1475. https://doi.org/10.3390/ijms20061475
24. Li Y, Shi B, Dong F, Zhu X, Liu B, Liu Y. LncRNA KCNQ1OT1 facilitates the progression of bladder cancer by targeting MiR-218-5p/HS3ST3B1. Cancer Gene Ther. 2021;28(3):212–20. https://doi.org/10.1038/s41417-020-00211-6
25. Benhadou F, Mintoff D, del Marmol V. Psoriasis: Keratinocytes or immune cells – Which is the trigger? Dermatology. 2019;235(2):91–100. https://doi.org/10.1159/000495291
26. Ru Y, Li H, Zhang R, Luo Y, Song J, Kuai L, et al. Role of keratinocytes and immune cells in the anti-inflammatory effects of tripterygium wilfordii hook. f. in a murine model of psoriasis. Phytomedicine. 2020;77:153299. https://doi.org/10.1016/j.phymed.2020.153299
27. He Q, Liu N, Hu F, Shi Q, Pi X, Chen H, et al. Circ_0061012 contributes to IL-22-induced proliferation, migration and invasion in keratinocytes through miR-194-5p/GAB1 axis in psoriasis. Biosci Rep. 2021;41(1):BSR20203130.