Skip to main content
Log in

Regulation of human β-galactoside α2,6-sialyltransferase (hST6Gal I) gene expression during differentiation of human osteoblastic MG-63 cells

  • Original Article
  • Published:
Glycoconjugate Journal Aims and scope Submit manuscript

Abstract

In this study, we found that gene expression of the human β-galactoside α2,6-sialyltransferase (hST6Gal I) was specifically increased during differentiation of human MG-63 osteoblastic cells by serum starvation (SS). In parallel, a distinct increase in binding to SNA, the α2,6-sialyl-specific lectin, was observed in serum-starved cells, as demonstrated by FACS analysis. 5’-Rapid amplification of cDNA ends analysis demonstrated that the increase of hST6Gal I transcript by SS is mediated by P1 promoter. To elucidate transcriptional regulation of hST6Gal I in SS-induced MG-63 cells, we functionally characterized the P1 promoter region of the hST6Gal I gene. The 5’-deletion analysis of P1 promoter region revealed that the 189 bp upstream region of transcription start site is critical for transcriptional activity of hST6Gal I gene in SS-induced MG-63 cells. This region contains the predicted binding sites for several transcription factors, including AREB6, FOXP1, SIX3, HNF1, YY2, and MOK2. The mutagenesis analysis for these sites and chromatin immunoprecipitation assay demonstrated that the YY2 binding site at -98 to -77 was essential for the SS-induced hST6Gal I gene expression during differentiation of MG-63 cells.

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. Dall’Olio, F.: The sialyl-α2,6-lactosaminyl-structure: biosynthesis and functional role. Glycoconj. J. 17, 669–676 (2000)

    Article  Google Scholar 

  2. Dall’Olio, F., Chiricolo, M.: Sialyltransferases in cancer. Glycoconj. J. 18, 841–850 (2001)

    Article  Google Scholar 

  3. Lu, J., Gu, J.: Significance of β-galactoside α2,6 sialyltranferase 1 in cancers. Molecules. 20, 7509–7527 (2015)

    Article  CAS  Google Scholar 

  4. Dall’Olio, F., Malagolini, N., di Stefano, G., Minni, F., Marrano, D., Serafini-Cessi, F.: Increased CMP-NeuAc:Gal β1,4GlcNAc-R α2,6 sialyltransferase activity in human colorectal cancer tissues. Int. J. Cancer. 44, 434–439 (1989)

    Article  Google Scholar 

  5. Gessner, P., Riedl, S., Quentmaier, A., Kemmner, W.: Enhanced activity of CMP-NeuAc:Galβ1-4GlcNAc:α2,6-sialyltransferase in metastasizing human colorectal tumor tissue and serum of tumor patients. Cancer Lett. 5, 143–149 (1993)

    Article  Google Scholar 

  6. Recchi, M.A., Hebbar, M., Hornez, L., Harduin-Lepers, A., Peyrat, J.P., Delannoy, P.: Multiplex reverse transcription polymerase chain reaction assessment of sialyltransferase expression in human breast cancer. Cancer Res. 58, 4066–4070 (1998)

    CAS  PubMed  Google Scholar 

  7. Recchi, M.A., Harduin-Lepers, A., Boilly-Marer, Y., Verbert, A., Delannoy, P.: Multiplex RT-PCR method for the analysis of the expression of human sialyltransferases: application to breast cancer cells. Glycoconj J. 15, 19–27 (1998)

    Article  CAS  Google Scholar 

  8. Dall’Olio, F., Chiricolo, M., D’Errico, A., Gruppioni, E., Altimari, A., Fiorentino, M., Grigioni, W.F.: Expression of β-galactoside α2,6 sialyltransferase and of α2,6-sialylated glycoconjugates in normal human liver, hepatocarcinoma, and cirrhosis. Glycobiology. 14, 39–49 (2004)

    Article  Google Scholar 

  9. Wang, P.H., Li, Y.F., Juang, C.M., Lee, Y.R., Chao, H.T., Tsai, Y.C., Yuan, C.C.: Altered mRNA expression of sialyltransferase in squamous cell carcinomas of the cervix. Gynecol. Oncol. 83, 121–127 (2001)

    Article  CAS  Google Scholar 

  10. Kaneko, Y., Yamamoto, H., Kersey, D.S., Colley, K.J., Leestma, J.E., Moskal, J.R.: The expression of Galβ1,4GlcNAc α2,6 sialyltransferase and α2,6-linked sialoglycoconjugates in human brain tumors. Acta Neuropathol. 91, 284–292 (1996)

    Article  CAS  Google Scholar 

  11. Fukushima, K., Hara-Kuge, S., Seko, A., Ikehara, Y., Yamashita, K.: Elevation of α2→6 sialyltransferase and α1→2 fucosyltransferase activities in human choriocarcinoma. Cancer Res. 58, 4301–4306 (1998)

    CAS  PubMed  Google Scholar 

  12. Skacel, P.O., Edwards, A.J., Harrison, C.T., Watkins, W.M.: Enzymic control of the expression of the X determinant (CD15) in human myeloid cells during maturation: the regulatory role of 6- sialytransferase. Blood 78, 1452–1460 (1991)

    Article  CAS  Google Scholar 

  13. Dall’Olio, F., Chiricolo, M., Lau, J.T.Y.: Differential expression of the hepatic transcript of β-galactoside α2,6 sialyltransferase in human colon cancer cell lines. Int. J. Cancer. 81, 243–247 (1999)

    Article  Google Scholar 

  14. Aas-Eng, D.A., Asheim, H.C., Deggerdal, A., Smeland, E., Funderud, S.: Characterization of a promoter region supporting transcription of a novel human β-galactoside α-2,6-sialyltransferase transcript in HepG2 cells. Biochim. Biophys. Acta 14, 166–169 (1995)

    Article  Google Scholar 

  15. Taniguchi, A., Hasegawa, Y., Higai, K., Matsumoto, K.: Transcriptional regulation of human β-galactoside α2,6-sialyltransferase (hST6Gal I) gene during differentiation of the HL-60 cell line. Glycobiology. 10, 623–628 (2000)

    Article  CAS  Google Scholar 

  16. Wang, X., Vertino, A., Eddy, R.L., Byers, M.G., Jani-Sait, S.N., Shows, T.B., Lau, J.T.: Chromosome mapping and organization of the human β-galactoside α2,6-sialyltransferase gene. Differential and cell-type specific usage of upstream exon sequences in B-lymphoblastoid cells. J. Biol. Chem. 268, 4355–4361 (1993)

    CAS  PubMed  Google Scholar 

  17. Lo, N.W., Lau, J.T.: Transcription of the β-galactoside α2,6 sialyltransferase gene in B lymphocytes is directed by a separate and distinct promoter. Glycobiology. 6, 271–279 (1996)

    Article  CAS  Google Scholar 

  18. Xu, L., Kurusu, Y., Takizawa, K., Tanaka, J., Matsumoto, K., Taniguchi, A.: Transcriptional regulation of human β-galactoside α2,6-sialyltransferase (hST6Gal I) gene in colon adenocarcinoma cell line. Biochem. Biophys. Res. Commun. 307, 1070–1074 (2003)

    Article  CAS  Google Scholar 

  19. Grundmann, U., Nerlich, C., Rein, T., Zettlmeissl, G.: Complete cDNA sequence encoding human β-galactoside α-2,6-sialyltransferase. Nucleic Acids Res. 18, 667–668 (1990)

    Article  CAS  Google Scholar 

  20. Wang, P.H., Lee, W.L., Lee, Y.R., Juang, C.M., Chen, Y.J., Chao, H.T., Tsai, Y.C., Yuan, C.C.: Enhanced expression of α2,6 sialyltransferase ST6Gal I in cervical squamous cell carcinoma. Gynecol. Oncol. 89, 395–401 (2003)

    Article  CAS  Google Scholar 

  21. Nakashima, K., de Crombrugghe, B.: Transcriptional mechanisms in osteoblast differentiation and bone formation. Trends Genet. 19, 458–466 (2003)

    Article  CAS  Google Scholar 

  22. Kihara, T., Ichikawa, S., Yonezawa, T., Lee, J.W., Akihisa, T., Woo, J.T., Michi, Y., Amagasa, T., Yamaguchi, A.: Acerogenin A, a natural compound isolated from Acer nikoense Maxim, stimulates osteoblast differentiation through bone morphogenetic protein action. Biochem. Biophys. Res. Commun. 406, 211–217 (2011)

    Article  CAS  Google Scholar 

  23. Yoon, H.K., Lee, J.W., Kim, K.S., Mun, S.W., Kim, D.H., Kim, H.J., Kim, C.H., Lee, Y.C.: Serum deprivation-induced human GM3 synthase (hST3Gal V) gene expression is mediated by Runx2 in human osteoblastic MG-63 cells. Int. J. Mol. Sci. 17, E35 (2015)

    Article  Google Scholar 

  24. Svensson, E.C., Conley, P.B., Paulson, J.C.: Regulated expression of α2,6-sialyltransferase by the liver-enriched transcription factors HNF-1, DBP, and LAP. J. Biol. Chem. 267, 3466–3472 (1992)

    CAS  PubMed  Google Scholar 

  25. Nguyen, N., Zhang, X., Olashaw, N., Seto, E.: Molecular cloning and functional characterization of the transcription factor YY2. J. Biol. Chem. 279, 25927–25934 (2004)

    Article  CAS  Google Scholar 

  26. Gordon, S., Akopyan, G., Garban, H., Bonavida, B.: Transcription factor YY1: structure, function, and therapeutic implications in cancer biology. Oncogene. 25, 1125–1142 (2006)

    Article  CAS  Google Scholar 

  27. Wang, C.C., Chen, J.J., Yang, P.C.: Multifunctional transcription factor YY1: a therapeutic target in human cancer? . Expert Opin. Ther. Targets. 10, 253–266 (2006)

    Article  CAS  Google Scholar 

  28. Behera, A.K., Kumar, M., Shanmugam, M.K., Bhattacharya, A., Rao, V.J., Bhat, A., et al.: Functional interplay between YY1 and CARM1 promotes oral carcinogenesis. Oncotarget. 10, 3709–3724 (2019)

    Article  Google Scholar 

  29. Meng, Q., Ren, C., Wang, L., Zhao, Y., Wang, S.: Knockdown of ST6Gal-I inhibits the growth and invasion of osteosarcoma MG-63 cells. Biomed. Pharmacother. 72, 172–178 (2015)

    Article  CAS  Google Scholar 

  30. Kasim, V., Xie, Y.D., Wang, H.M., Huang, C., Yan, X.S., Nian, W.Q., Zheng, X.D., Miyagishi, M., Wu, S.R.: Transcription factor Yin Yang 2 is a novel regulator of the p53/p21 axis. Oncotarget. 8, 54694–54707 (2017)

    Article  Google Scholar 

  31. Tahmasebi, S., Jafarnejad, S.M., Tam, I.S., Gonatopoulos-Pournatzis, T., Matta-Camacho, E., Tsukumo, Y., et al.: Control of embryonic stem cell selfrenewal and differentiation via coordinated alternative splicing and translation of YY2. Proc. Natl. Acad. Sci. USA 113, 12360–12367 (2016)

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by the Dong-A University research fund.

Author information

Authors and Affiliations

Authors

Contributions

Conceived and designed the experiments: Miri Lee, Cheorl-Ho Kim, Young-Choon. Performed the experiments: Miri Lee, So-Young An, Hyun-Kyoung Yoon. Analyzed the data: Miri Lee, So-Young An, Hyun-Kyoung Yoon, Kyoung-Sook Kim, Dong-Hyun Kim, Cheorl-Ho Kim, Young-Choon Lee. Contributed reagents/materials/analysis tools: Dong-Hyun Kim, Hyun-Jun Kim, Kichoon Lee, Cheorl-Ho Kim. Wrote the paper: Miri Lee, Cheorl-Ho Kim, Young-Choon Lee.

Corresponding authors

Correspondence to Cheorl-Ho Kim or Young-Choon Lee.

Ethics declarations

Conflict of interest

The authors did not declare any competing interests in this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Ethical approval

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

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

An, SY., Lee, M., Yoon, HK. et al. Regulation of human β-galactoside α2,6-sialyltransferase (hST6Gal I) gene expression during differentiation of human osteoblastic MG-63 cells. Glycoconj J 37, 681–690 (2020). https://doi.org/10.1007/s10719-020-09959-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10719-020-09959-3

Keywords

Navigation