Silencing FUT4 Inhibits the Progression of Osteosarcoma through Activation of FOXO1


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Abstract

Background:It has been reported that inhibition of Fucosyltransferase4 (FUT4) to activate Forkhead box O1 (FOXO1) can lead to apoptosis of cancer cells, however, the mechanism in osteosarcoma is still unclear.

Objective:To explore the biological significance of the connection between FUT4 and FOXO1 in osteosarcoma growth.

Methods:In vitro tests were conducted using the human osteoblast cell line and the osteosarcoma cell lines. QRT-PCR assay as well as western blot assay were used to ascertain the relative expression levels of FUT4 and FOXO1 in the cells. By using the CCK-8 assay, colony assay, EDU assay, wound healing assay and Transwell assay, osteosarcoma cells' ability to proliferate, migrate and invade were examined in relation to si- FUT4. TUNEL test was used to evaluate Si-impact FUT4's on KHOS and U2OS apoptosis in osteosarcoma cells. Western blot assay was used to identify the expression of proliferative, migrating and apoptosis-related protein markers in osteosarcoma cells KHOS and U2OS and the expression of important proteins in the Wnt/ β-catenin signaling pathway.

Results:In comparison with osteoblasts, osteosarcoma cells expressed more FUT4. The osteosarcoma cells' capacities to proliferate, invade, and migrate were markedly inhibited by the inhibition of FUT4 expression, which also increased osteosarcoma cell apoptosis. The Wnt/β-catenin signaling pathway was blocked by upregulating FOXO1 expression, which was in turn inhibited by inhibiting FUT4 expression.

Conclusion:Osteosarcoma cells express more FUT4. The Wnt/β-catenin signaling pathway has a significant effect on osteosarcoma cell death, and inhibition of FUT4 expression may target FOXO1 activation to decrease osteosarcoma cells' ability to proliferate, invade, and migrate.

About the authors

Yang Yang

Department of Trauma Center,, Affiliated Hospital of Nantong University, Nantong City

Email: info@benthamscience.net

Xiaodi Yan

Department of Radiation Oncology, Affiliated Hospital of Nantong University, Nantong City

Email: info@benthamscience.net

YueYuan Chen

Department of Oncology, Second People’s Hospital of Nantong & Affiliated Nantong Rehabilitation Hospital of Nantong University

Email: info@benthamscience.net

Jiajia Liu

Department of Trauma Center, Affiliated Hospital of Nantong University, Nantong City

Email: info@benthamscience.net

Jianhua Xue

Department of Trauma Center, Affiliated Hospital of Nantong University, Nantong City

Email: info@benthamscience.net

Xiaoming Sheng

Department of Trauma Center, Affiliated Hospital of Nantong University, Nantong City

Email: info@benthamscience.net

Jun Qin

Department of Trauma Center, Affiliated Hospital of Nantong University, Nantong City

Email: info@benthamscience.net

Qiang Xue

Department of Radiation Oncology, Affiliated Hospital of Nantong University, Nantong City

Author for correspondence.
Email: info@benthamscience.net

Xianchen Liu

Department of Radiation Oncology, Affiliated Hospital of Nantong University, Nantong City

Author for correspondence.
Email: info@benthamscience.net

References

  1. Wu PK, Chen WM, Lee OK, Chen CF, Huang CK, Chen TH. The prognosis for patients with osteosarcoma who have received prior manipulative therapy. J Bone Joint Surg Br 2010; 92-B(11): 1580-5. doi: 10.1302/0301-620X.92B11.24706 PMID: 21037356
  2. Huang YF, Lu L, Shen HL, Lu XX. Retracted: LncRNA SNHG4 promotes osteosarcoma proliferation and migration by sponging miR-377-3p. Mol Genet Genomic Med 2020; 8(8): e1349. doi: 10.1002/mgg3.1349 PMID: 32537941
  3. Harrison DJ, Geller DS, Gill JD, Lewis VO, Gorlick R. Current and future therapeutic approaches for osteosarcoma. Expert Rev Anticancer Ther 2018; 18(1): 39-50. doi: 10.1080/14737140.2018.1413939 PMID: 29210294
  4. Sun C, Chen C, Chen Z, et al. MicroRNA-181a-5p promotes osteosarcoma progression via PTEN/AKT pathway. Anal Cell Pathol (Amst) 2022; 2022: 1-13. doi: 10.1155/2022/3421600 PMID: 35310933
  5. Cong J, Gong J, Yang C, Xia Z, Zhang H. Retracted article: MiR-200c/FUT4 axis prevents the proliferation of colon cancer cells by downregulating the Wnt/β-catenin pathway. BMC Cancer 2021; 21(1): 2. doi: 10.1186/s12885-020-07670-y PMID: 33397320
  6. Liu B, Ma H, Liu Q, et al. MiR-29b/Sp1/FUT4 axis modulates the malignancy of leukemia stem cells by regulating fucosylation via Wnt/β-catenin pathway in acute myeloid leukemia. J Exp Clin Cancer Res 2019; 38(1): 200. doi: 10.1186/s13046-019-1179-y PMID: 31097000
  7. Zhang Y, Zhang D, Lv J, Wang S, Zhang Q. MiR-125a-5p suppresses bladder cancer progression through targeting FUT4. Biomed Pharmacother 2018; 108: 1039-47. doi: 10.1016/j.biopha.2018.09.100 PMID: 30372804
  8. Hu J, Wang Z, Pan Y, et al. MiR-26a and miR-26b mediate osteoarthritis progression by targeting FUT4 via NF-κB signaling pathway. Int J Biochem Cell Biol 2018; 94: 79-88. doi: 10.1016/j.biocel.2017.12.003 PMID: 29208566
  9. Chen R, Zhang X, Wang C. LncRNA HOXB-AS1 promotes cell growth in multiple myeloma via FUT4 mRNA stability by ELAVL1. J Cell Biochem 2020; 121(10): 4043-51. doi: 10.1002/jcb.29573 PMID: 31886581
  10. Williams CB, Chatila TA. Fox family ties. Cell Res 2013; 23(4): 452-4. doi: 10.1038/cr.2013.5 PMID: 23318581
  11. Guo LT, Wang SQ, Su J, et al. Baicalin ameliorates neuroinflammation-induced depressive-like behavior through inhibition of toll-like receptor 4 expression via the PI3K/AKT/FoxO1 pathway. J Neuroinflammation 2019; 16(1): 95. doi: 10.1186/s12974-019-1474-8 PMID: 31068207
  12. Li K, Deng Y, Deng G, et al. High cholesterol induces apoptosis and autophagy through the ROS-activated AKT/FOXO1 pathway in tendon-derived stem cells. Stem Cell Res Ther 2020; 11(1): 131. doi: 10.1186/s13287-020-01643-5 PMID: 32197645
  13. Gao W, Liang J, Ye Y, et al. FUT4siRNA augments the chemosensitivity of non-small cell lung cancer to cisplatin through activation of FOXO1-induced apoptosis. BMC Cancer 2020; 20(1): 895. doi: 10.1186/s12885-020-07324-z PMID: 32948132
  14. Ottaviani G, Jaffe N. The epidemiology of osteosarcoma. Cancer Treat Res 2009; 152: 3-13. doi: 10.1007/978-1-4419-0284-9_1 PMID: 20213383
  15. Meyer WH. Recent developments in genetic mechanisms, assessment, and treatment of osteosarcomas. Curr Opin Oncol 1991; 3(4): 689-93. PMID: 1932229
  16. Gorlick R, Khanna C. Osteosarcoma. J Bone Miner Res 2010; 25(4): 683-91. doi: 10.1002/jbmr.77 PMID: 20205169
  17. Xue Q, Yang Y, Yang L, et al. miR-371b-5p-engineered exosomes enhances tumor inhibitory effect. Front Cell Dev Biol 2021; 9: 750171. doi: 10.3389/fcell.2021.750171 PMID: 34671604
  18. Tian C, Sun X, Han K, Zhu H, Min D, Lin S. Long Non-coding RNA MRUL contributes to osteosarcoma progression through the miR-125a-5p/FUT4 Axis. Front Genet 2020; 11: 672. doi: 10.3389/fgene.2020.00672 PMID: 32670359
  19. Fang F, VanCleave A, Helmuth R, et al. Targeting the Wnt/β- catenin pathway in human osteosarcoma cells. Oncotarget 2018; 9(95): 36780-92. doi: 10.18632/oncotarget.26377 PMID: 30613366
  20. Chu W, Cao L, Daokun G, Zhao J. iNOS promotes the development of osteosarcoma via Wnt/β-catenin pathway. J Immunol Res 2021; 2021: 1-10. doi: 10.1155/2021/4549221 PMID: 34435052
  21. Liao Y, Sassi S, Halvorsen S, et al. Androgen receptor is a potential novel prognostic marker and oncogenic target in osteosarcoma with dependence on CDK11. Sci Rep 2017; 7(1): 43941. doi: 10.1038/srep43941 PMID: 28262798
  22. Morelli A, Comeglio P, Filippi S, et al. Testosterone and farnesoid X receptor agonist INT-747 counteract high fat diet-induced bladder alterations in a rabbit model of metabolic syndrome. J Steroid Biochem Mol Biol 2012; 132(1-2): 80-92. doi: 10.1016/j.jsbmb.2012.02.007 PMID: 22406511
  23. Dong X, Cai C, Fu T. FXR suppresses colorectal cancer by inhibiting the Wnt/β-catenin pathway via activation of TLE3. Genes Dis 2023; 10(3): 719-22. doi: 10.1016/j.gendis.2022.09.006 PMID: 37396519
  24. Ponnampalam AP, Rogers PAW. Expression and regulation of fucosyltransferase 4 in human endometrium. Reproduction 2008; 136(1): 117-23. doi: 10.1530/REP-07-0548 PMID: 18367501
  25. Roberts RD. Is estrogen the answer for osteosarcoma? Cancer Res 2019; 79(6): 1034-5. doi: 10.1158/0008-5472.CAN-19-0209 PMID: 30877098

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