PLoS ONE (Jan 2011)

MicroRNA let-7f inhibits tumor invasion and metastasis by targeting MYH9 in human gastric cancer.

  • Shuli Liang,
  • Lijie He,
  • Xiaodi Zhao,
  • Yu Miao,
  • Yong Gu,
  • Changcun Guo,
  • Zengfu Xue,
  • Weijia Dou,
  • Fengrong Hu,
  • Kaichun Wu,
  • Yongzhan Nie,
  • Daiming Fan

DOI
https://doi.org/10.1371/journal.pone.0018409
Journal volume & issue
Vol. 6, no. 4
p. e18409

Abstract

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BACKGROUND: MicroRNAs (miRNAs) are important regulators that play key roles in tumorigenesis and tumor progression. A previous report has shown that let-7 family members can act as tumor suppressors in many cancers. Through miRNA array, we found that let-7f was downregulated in the highly metastatic potential gastric cancer cell lines GC9811-P and SGC7901-M, when compared with their parental cell lines, GC9811 and SGC7901-NM; however, the mechanism was not clear. In this study, we investigate whether let-7f acts as a tumor suppressor to inhibit invasion and metastasis in gastric cancers. METHODOLOGY/PRINCIPAL: Real-time PCR showed decreased levels of let-7f expression in metastatic gastric cancer tissues and cell lines that are potentially highly metastatic. Cell invasion and migration were significantly impaired in GC9811-P and SGC7901-M cell lines after transfection with let-7f-mimics. Nude mice with xenograft models of gastric cancer confirmed that let-7f could inhibit gastric cancer metastasis in vivo after transfection by the lentivirus pGCsil-GFP- let-7f. Luciferase reporter assays demonstrated that let-7f directly binds to the 3'UTR of MYH9, which codes for myosin IIA, and real-time PCR and Western blotting further indicated that let-7f downregulated the expression of myosin IIA at the mRNA and protein levels. CONCLUSIONS/SIGNIFICANCE: Our study demonstrated that overexpression of let-7f in gastric cancer could inhibit invasion and migration of gastric cancer cells through directly targeting the tumor metastasis-associated gene MYH9. These data suggest that let-7f may be a novel therapeutic candidate for gastric cancer, given its ability to reduce cell invasion and metastasis.