Original Paper

miR-124 inhibits cell proliferation in gastric cancer through down-regulation of SPHK1†

  1. Jintang Xia1,2,‡,
  2. Zhiqiang Wu3,‡,
  3. Chunping Yu4,
  4. Weiling He5,
  5. Haiqing Zheng6,
  6. Yulong He5,
  7. Weihua Jian1,2,
  8. Lianzhou Chen1,
  9. Luanjing Zhang1,
  10. Wen Li1,*

Article first published online: 23 MAY 2012

DOI: 10.1002/path.4030

Issue

The Journal of Pathology

The Journal of Pathology

Volume 227, Issue 4, pages 470–480, August 2012

Additional Information

How to Cite

Xia, J., Wu, Z., Yu, C., He, W., Zheng, H., He, Y., Jian, W., Chen, L., Zhang, L. and Li, W. (2012), miR-124 inhibits cell proliferation in gastric cancer through down-regulation of SPHK1. J. Pathol., 227: 470–480. doi: 10.1002/path.4030

Author Information

  1. 1

    Laboratory of Department of Surgery, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China

  2. 2

    Department of Hepatobiliary Surgery, Guangzhou First Municipal People's Hospital Affiliated to Guangzhou Medical College, Guangzhou, Guangdong, People's Republic of China

  3. 3

    Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China

  4. 4

    State Key Laboratory of Oncology in Southern China, Department of Experimental Research, Cancer Centre, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China

  5. 5

    Department of Gastrointestinal Surgery, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China

  6. 6

    Department of Rehabilitation Medicine, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China

  1. ‡

    These authors contributed equally to this study.

*Laboratory of Department of Surgery, First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Road, Guangzhou, Guangdong 510080, People's Republic of China.

  1. †

    No conflicts of interest were declared.

  2. ‡

    These authors contributed equally to this study.

Publication History

  1. Issue published online: 10 JUL 2012
  2. Article first published online: 23 MAY 2012
  3. Accepted manuscript online: 27 MAR 2012 04:00AM EST
  4. Manuscript Accepted: 20 MAR 2012
  5. Manuscript Revised: 15 MAR 2012
  6. Manuscript Received: 25 JUL 2011

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Keywords:

  • SPHK1;
  • miR-124;
  • gastric cancer;
  • proliferation;
  • FOXO1

Abstract

SPHK1 expression is elevated in gastric cancer and is associated with shorter survival times for patients. However, the molecular mechanism of SPHK1 up-regulation in gastric cancer remains unclear. In the present study, we report that miR-124 down-regulated SPHK1 expression by directly targeting its 3′-untranslated region (3′-UTR) and that miR-124 expression was inversely correlated with SPHK1 expression in gastric cancer samples. Furthermore, we demonstrated that, similar to the effect of silencing SPHK1, up-regulation of miR-124 markedly inhibited proliferation and tumourigenicity of gastric cancer cells both in vitro and in vivo. This was found to be mechanistically associated with induction of cyclin-dependent kinase inhibitors p21equation image and p27equation image, enhancement of the transcriptional activity of FOXO1 and suppression of AKT activity. Moreover, we showed that the re-introduction of SPHK1 (without the 3′-UTR), but not with the 3′-UTR, could abrogate the miR-124-mediated induction of p21equation image and p27equation image, as well as rescue the miR-124-induced proliferation inhibition. Together, these results suggest that miR-124 has an important role in the suppression of gastric cancer and presents a novel mechanism of miRNA-mediated SPHK1 expression in cancer cells. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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