Skip to main content
Log in

Hsa-miR-370 inhibited P-selectin-induced cell adhesion in human colon adenocarcinoma cells

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Sialyl Lewis x (sLex) is a minimal recognition motif for ligands of P-selectin and plays an important role in tumor cell adhesion and migration. Thus, targeting sLex could be an effective method to prevent tumor metastasis. In this study, we aimed to identify a microRNA (miRNA) which is capable to suppress the expression of sLex. MicroRNAs which may target ST3GAL4 were predicted by the online tools. Colo 320 HSR human colon adenocarcinoma cells were employed. The transcriptional and translational levels of ST3GAL4 were evaluated by western blotting and Real-time quantitative polymerase chain reaction. Cell adhesion and spread were assessed with or without hsa-miR-370 treatment. It was shown that hsa-miR-370 inhibited the expression of sLex in colo-320 cells, which repressed the binding of P-selectin, and led to reduced cell attachment and spread. Our results found that P-selectin-induced elevations of p-p38 and p-PI3K levels were significantly inhibited by hsa-miR-370, indicating that repressed sLex level is able to reduce the P-selectin binding and therefore eliminating the P-selectin-induced activation of p38 and PI3K signaling. In conclusion, we found that hsa-miR-370 specifically inhibits the expression of sLex, represses cell adhesion and spreading in colo-320 cells. Our study provides a possible effective treatment against tumor invasion.

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

Access this article

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

Instant access to the full article PDF.

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

Similar content being viewed by others

References

  1. McEver RP (2015) Selectins: initiators of leucocyte adhesion and signalling at the vascular wall. Cardiovasc Res 107:331–339. https://doi.org/10.1093/cvr/cvv154

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Chen M, Geng JG (2006) P-selectin mediates adhesion of leukocytes, platelets, and cancer cells in inflammation, thrombosis, and cancer growth and metastasis. Arch Immunol Ther Exp 54:75–84. https://doi.org/10.1007/s00005-006-0010-6

    Article  CAS  Google Scholar 

  3. Mcever RP, Beckstead JH, Moore KL, Marshallcarlson L, Bainton DF (1989) Gmp-140, a platelet alpha-granule membrane-protein, is also synthesized by vascular endothelial-cells and is localized in Weibel-Palade bodies. J Clin Invest 84:92–99. https://doi.org/10.1172/Jci114175

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Spertini C, Baisse B, Spertini O (2012) Ezrin-radixin-moesin-binding sequence of PSGL-1 glycoprotein regulates leukocyte rolling on selectins and activation of extracellular signal-regulated kinases. J Biol Chem 287:10693–10702. https://doi.org/10.1074/jbc.M111.318022

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Totani L, Evangelista V (2010) Platelet-leukocyte interactions in cardiovascular disease and beyond. Arterioscler Thromb Vasc Biol 30:2357–2361. https://doi.org/10.1161/Atvbaha.110.207480

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Palumbo JS, Talmage KE, Massari JV, La Jeunesse CM, Flick MJ, Kombrinck KW, Jirouskova M, Degen JL (2005) Platelets and fibrin(ogen) increase metastatic potential by impeding natural killer cell-mediated elimination of tumor cells. Blood 105:178–185. https://doi.org/10.1182/blood-2004-06-2272

    Article  CAS  PubMed  Google Scholar 

  7. Ho-Tin-Noe B, Goerge T, Wagner DD (2009) Platelets: guardians of tumor vasculature. Cancer Res 69:5623–5626. https://doi.org/10.1158/0008-5472.Can-09-1370

    Article  CAS  PubMed  Google Scholar 

  8. Cattaneo MG, Codignola A, Vicentini LM, Clementi F, Sher E (1993) Nicotine stimulates a serotonergic autocrine loop in human small-cell lung-carcinoma. Cancer Res 53:5566–5568

    CAS  PubMed  Google Scholar 

  9. Natoni A, Macauley MS, O’Dwyer ME (2016) Targeting selectins and their ligands in cancer. Front Oncol. https://doi.org/10.3389/fonc.2016.00093

    Article  PubMed  PubMed Central  Google Scholar 

  10. Gomes C, Osorio H, Pinto MT, Campos D, Oliveira MJ, Reis CA (2013) Expression of ST3GAL4 leads to SLe(x) expression and induces c-Met activation and an invasive phenotype in gastric carcinoma cells. PLoS ONE 8:e66737. https://doi.org/10.1371/journal.pone.0066737

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Fukuda MN, Ohyama C, Lowitz K, Matsuo O, Pasqualini R, Ruoslahti E, Fukuda M (2000) A peptide mimic of E-selectin ligand inhibits sialyl Lewis X-dependent lung colonization of tumor cells. Cancer Res 60:450–456

    CAS  PubMed  Google Scholar 

  12. Ip CK, Li S, Tang MY, Sy S, Shum H, Wong AS (2015) Sialyl Lewis x is essential for early stage ovarian tumor metastasis through modulation of tumor-mesothelial adhesion. Mol Biol Cell 26: Meeting Abstract: P1086

  13. Kefas B, Godlewski J, Comeau L, Li YQ, Abounader R, Hawkinson M, Lee JW, Fine H, Chiocca EA, Lawler S, Purow B (2008) microRNA-7 inhibits the epidermal growth factor receptor and the Akt pathway and is down-regulated in glioblastoma. Cancer Res 68:3566–3572. https://doi.org/10.1158/0008-5472.Can-07-6639

    Article  CAS  PubMed  Google Scholar 

  14. Whittard JD, Akiyama SK (2001) Activation of beta1 integrins induces cell-cell adhesion. Exp Cell Res 263:65–76. https://doi.org/10.1006/excr.2000.5099

    Article  CAS  PubMed  Google Scholar 

  15. Bendas G, Borsig L (2012) Cancer cell adhesion and metastasis: selectins, integrins, and the inhibitory potential of heparins. Int J Cell Biol. https://doi.org/10.1155/2012/676731

    Article  PubMed  PubMed Central  Google Scholar 

  16. Kim YJ, Borsig L, Varki NM, Varki A (1998) P-selectin deficiency attenuates tumor growth and metastasis. Proc Natl Acad Sci USA 95:9325–9330. https://doi.org/10.1073/pnas.95.16.9325

    Article  CAS  PubMed  Google Scholar 

  17. Kim YJ, Borsig L, Han HL, Varki NM, Varki A (1999) Distinct selectin ligands on colon carcinoma mucins can mediate pathological interactions among platelets, leukocytes, and endothelium. Am J Pathol 155:461–472. https://doi.org/10.1016/S0002-9440(10)65142-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Mannori G, Crottet P, Cecconi O, Hanasaki K, Aruffo A, Nelson RM, Varki A, Bevilacqua MP (1995) Differential colon cancer cell adhesion to E-, P-, and L-selectin: role of mucin-type glycoproteins. Cancer Res 55:4425–4431

    CAS  PubMed  Google Scholar 

  19. Kannagi R, Izawa M, Koike T, Miyazaki K, Kimura N (2004) Carbohydrate-mediated cell adhesion in cancer metastasis and angiogenesis. Cancer Sci 95:377–384. https://doi.org/10.1111/j.1349-7006.2004.tb03219.x

    Article  CAS  PubMed  Google Scholar 

  20. St Hill CA (2011) Interactions between endothelial selectins and cancer cells regulate metastasis. Front Biosci-Landmark 16:3233–3251. https://doi.org/10.2741/3909

    Article  CAS  Google Scholar 

  21. Borsig L, Stevenson JL, Varki A (2007) Heparin in cancer: role of selectin interactions. New findings in translational science, cancer-associated thrombosis, prevention, and treatment, p 97

  22. Portela SV, Martin CV, Romay LM, Cuevas E, Martin EG, Briera AF (2011) sLea and sLex expression in colorectal cancer: implications for tumourigenesis and disease prognosis. Histol Histopathol 26:1305–1316. https://doi.org/10.14670/hh-26.1305

    Article  PubMed  Google Scholar 

  23. Jeschke U, Mylonas I, Shabani N, Kunert-Keil C, Schindlbeck C, Gerber B, Friese K (2005) Expression of Sialyl Lewis X, Sialyl Lewis a, E-cadherin and cathepsin-D in human breast cancer: immunohistochemical analysis in mammary carcinoma in situ, invasive carcinomas and their lymph node metastasis. Anticancer Res 25:1615–1622

    CAS  PubMed  Google Scholar 

  24. Mizuguchi S, Nishiyama N, Iwata T, Nishida T, Izumi N, Tsukioka T, Inoue K, Kameyama M, Suehiro S (2007) Clinical value of serum cytokeratin 19 fragment and sialyl-Lewis x in non-small cell lung cancer. Ann Thorac Surg 83:216–222. https://doi.org/10.1016/j.athoracsur.2006.08.042

    Article  PubMed  Google Scholar 

  25. Witz IP (2008) The selectin-selectin ligand axis in tumor progression. Cancer Metastasis Rev 27:19–30. https://doi.org/10.1007/s10555-007-9101-z

    Article  CAS  PubMed  Google Scholar 

  26. Laubli H, Borsig L (2010) Selectins promote tumor metastasis. Sem Cancer Biol 20:169–177. https://doi.org/10.1016/j.semcancer.2010.04.005

    Article  CAS  Google Scholar 

  27. Feng YM, Wang LX, Zeng JP, Shen L, Liang XM, Yu H, Liu SL, Liu ZF, Sun YD, Li WJ, Chen CY, Jia JH (2013) FoxM1 is overexpressed in helicobacter pylori-induced gastric carcinogenesis and is negatively regulated by miR-370. Mol Cancer Res 11:834–844. https://doi.org/10.1158/1541-7786.Mcr-13-0007

    Article  CAS  PubMed  Google Scholar 

  28. Li WJ, Cheng P, Nie SD, Cui W (2016) miR-370 mimic inhibits replication of Japanese encephalitis virus in glioblastoma cells. Neuropsychiatr Dis Treat 12:2411–2417. https://doi.org/10.2147/Ndt.S113236

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Liu Q, He HJ, Gu N, Han ZB, Xing YJ, Zeng TB, Huang ZJ, Wu Q (2013) miR-370 is stage-specifically expressed during mouse embryonic development and regulates Dnmt3a. FEBS Lett 587:775–781. https://doi.org/10.1016/j.febslet.2013.01.070

    Article  CAS  Google Scholar 

  30. Wang J (2013) Stat3 Inhibits WTX Expression through up-regulation of microRNA-370 in Wilms tumor. Pediatr Blood Cancer 60:32–33

    Article  Google Scholar 

  31. Reyes-Reyes ME, George MD, Roberts JD, Akiyama SK (2006) P-selectin activates integrin-mediated colon carcinoma cell adhesion to fibronectin. Exp Cell Res 312:4056–4069. https://doi.org/10.1016/j.yexcr.2006.09.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Simon SI, Hu Y, Vestweber D, Smith CW (2000) Neutrophil tethering on E-selectin activates beta(2) integrin binding to ICAM-1 through a mitogen-activated protein kinase signal transduction pathway. J Immunol 164:4348–4358. https://doi.org/10.4049/jimmunol.164.8.4348

    Article  CAS  PubMed  Google Scholar 

  33. Crocketttorabi E, Sulenbarger B, Smith CW, Fantone JC (1995) Activation of human neutrophils through L-selectin and Mac-1 molecules. J Immunol 154:2291–2302

    CAS  Google Scholar 

  34. Blanks JE, Moll T, Eytner R, Vestweber D (1998) Stimulation of P-selectin glycoprotein ligand-1 on mouse neutrophils activates beta(2)-integrin mediated cell attachment to ICAM-1. Eur J Immunol 28:433–443

    Article  CAS  PubMed  Google Scholar 

  35. Richard V, Pillai MR (2010) The stem cell code in oral epithelial tumorigenesis: the cancer stem cell shift hypothesis. Biochim Biophys Acta 1806:146–162. https://doi.org/10.1016/j.bbcan.2010.06.004

    Article  CAS  PubMed  Google Scholar 

  36. Stachurska A, Elbanowski J, Kowalczynska HM (2012) Role of alpha5beta1 and alphavbeta3 integrins in relation to adhesion and spreading dynamics of prostate cancer cells interacting with fibronectin under in vitro conditions. Cell Biol Int 36:883–892. https://doi.org/10.1042/cbi20110522

    Article  CAS  PubMed  Google Scholar 

  37. Kim WY, Jang JY, Jeon YK, Chung DH, Kim YG, Kim CW (2014) Syntenin increases the invasiveness of small cell lung cancer cells by activating p38, AKT, focal adhesion kinase and SP1. Exp Mol Med. https://doi.org/10.1038/emm.2014.1

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This study was supported by Social Development Project of Public Welfare Technology Research, from Science Technology Department of Zhejiang Province (2014C33137); Public Welfare Research Project, from Science Technology Department of Huzhou City (2010YSB08); Public Welfare Research Project, from Science Technology Department of Huzhou City (2017GY47).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yunhai Wei.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Research involving human participants and/or animals

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

Not applicable.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wei, Y., Shao, J., Wang, Y. et al. Hsa-miR-370 inhibited P-selectin-induced cell adhesion in human colon adenocarcinoma cells. Mol Cell Biochem 450, 159–166 (2019). https://doi.org/10.1007/s11010-018-3382-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-018-3382-0

Keywords

Navigation