miR-29b suppresses proliferation, migration, and invasion of tongue squamous cell carcinoma through PTEN-AKT signaling pathway by targeting Sp1

Oral Oncol. 2014 Nov;50(11):1062-71. doi: 10.1016/j.oraloncology.2014.07.010. Epub 2014 Aug 7.

Abstract

Objectives: miR-29b has been implicated in various cancers. However, the role of miR-29b in tongue squamous cell carcinoma (TSCC) remains unclear. This study aimed to investigate the role of miR-29b in TSCC progression.

Materials and methods: The expression of miR-29b was analyzed in TSCC tissues and cells. Functional studies were performed in TSCC cells. Real time-PCR, Western blot, cell proliferation, transwell, and dual luciferase reporter assays were performed according to standard procedures.

Results: miR-29b was significantly decreased in TSCC specimens and cell lines compared with corresponding normal counterparts. Overexpression of miR-29b significantly inhibited the proliferation, migration, invasion, and cell-cycle progression of TSCC cells, and promoted apoptosis. Moreover, miR-29b targeted the 3' untranslated region of the Sp1 transcript and resulted in the deregulation of Sp1. The inhibition of Sp1 by miR-29b subsequently resulted in the upregulation of PTEN, leading to a decline of phosphorylated AKT. Knockdown of Sp1 in TSCC cell lines mimicked the effects of miR-29b overexpression. In addition, the expression of miR-29b was inversely correlated with Sp1 and positively correlated with the PTEN in TSCC specimens.

Conclusion: miR-29b functions as a tumor suppressor in TSCC, and the miR-29b/Sp1/PTEN/AKT axis might represent a potential therapeutic target for TSCC intervention.

Keywords: AKT; Oral cancer; PTEN; Sp1; Tongue squamous cell carcinoma; miR-29b.

MeSH terms

  • Base Sequence
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology*
  • Cell Proliferation
  • DNA Primers
  • Humans
  • MicroRNAs / physiology*
  • Neoplasm Invasiveness*
  • Neoplasm Metastasis*
  • PTEN Phosphohydrolase / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction*
  • Sp1 Transcription Factor / metabolism*
  • Tongue Neoplasms / genetics
  • Tongue Neoplasms / metabolism
  • Tongue Neoplasms / pathology*

Substances

  • DNA Primers
  • MIRN29a microRNA, human
  • MicroRNAs
  • Sp1 Transcription Factor
  • Proto-Oncogene Proteins c-akt
  • PTEN Phosphohydrolase
  • PTEN protein, human