MicroRNA-9 suppresses cell migration and invasion through downregulation of TM4SF1 in colorectal cancer

  • Authors:
    • Young Ran Park
    • Soo Teik Lee
    • Se Lim Kim
    • Yu Chuan Liu
    • Min Ro Lee
    • Ja Hyun Shin
    • Seung Young Seo
    • Seong Hun Kim
    • In Hee Kim
    • Seung Ok Lee
    • Sang Wook Kim
  • View Affiliations

  • Published online on: March 9, 2016     https://doi.org/10.3892/ijo.2016.3430
  • Pages: 2135-2143
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Transmembrane-4-L6 family 1 (TM4SF1) is upregulated in colorectal carcinoma (CRC). However, the mechanism leading to inhibition of the TM4SF1 is not known. In the present study, we investigated the regulation of TM4SF1 and function of microRNAs (miRNAs) in CRC invasion and metastasis. We analyzed 60 colon cancers and paired normal specimens for TM4SF1 and miRNA-9 (miR-9) expression using quantitative real-time PCR. A bioinformatics analysis identified a putative miR-9 binding site within the 3'-UTR of TM4SF1. We also found that TM4SF1 was upregulated in CRC tissues and CRC cell lines. The expression of TM4SF1 was positively correlated with clinical advanced stage and lymph node metastasis. Moreover, a luciferase assay revealed that miR-9 directly targeted 3'-UTR-TM4SF1. Overexpression of miR-9 inhibited expression of TM4SF1 mRNA and protein, wound healing, transwell migration and invasion of SW480 cells, whereas, overexpression of anti-miR-9 and siRNA-TM4SF1 inversely regulated the TM4SF1 mRNA and protein level in HCT116 cells. Furthermore, miR-9 suppressed not only TM4SF1 expression but also MMP-2, MMP-9 and VEGF expression. In clinical specimens, miR-9 was generally down-regulated in CRC and inversely correlated with TM4SF1 expression. These results suggest that miR-9 functions as a tumor-suppressor in CRC, and that its suppressive effects mediate invasion and metastasis by inhibition of TM4SF1 expression. Our results also indicate that miR-9 might be a novel target for the treatment of CRC invasion and metastasis.
View Figures
View References

Related Articles

Journal Cover

May-2016
Volume 48 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Park YR, Lee ST, Kim SL, Liu YC, Lee MR, Shin JH, Seo SY, Kim SH, Kim IH, Lee SO, Lee SO, et al: MicroRNA-9 suppresses cell migration and invasion through downregulation of TM4SF1 in colorectal cancer. Int J Oncol 48: 2135-2143, 2016
APA
Park, Y.R., Lee, S.T., Kim, S.L., Liu, Y.C., Lee, M.R., Shin, J.H. ... Kim, S.W. (2016). MicroRNA-9 suppresses cell migration and invasion through downregulation of TM4SF1 in colorectal cancer. International Journal of Oncology, 48, 2135-2143. https://doi.org/10.3892/ijo.2016.3430
MLA
Park, Y. R., Lee, S. T., Kim, S. L., Liu, Y. C., Lee, M. R., Shin, J. H., Seo, S. Y., Kim, S. H., Kim, I. H., Lee, S. O., Kim, S. W."MicroRNA-9 suppresses cell migration and invasion through downregulation of TM4SF1 in colorectal cancer". International Journal of Oncology 48.5 (2016): 2135-2143.
Chicago
Park, Y. R., Lee, S. T., Kim, S. L., Liu, Y. C., Lee, M. R., Shin, J. H., Seo, S. Y., Kim, S. H., Kim, I. H., Lee, S. O., Kim, S. W."MicroRNA-9 suppresses cell migration and invasion through downregulation of TM4SF1 in colorectal cancer". International Journal of Oncology 48, no. 5 (2016): 2135-2143. https://doi.org/10.3892/ijo.2016.3430