MiR-378 promotes the cell proliferation of osteosarcoma through down-regulating the expression of Kruppel-like factor 9

Biochem Cell Biol. 2018 Oct;96(5):515-521. doi: 10.1139/bcb-2017-0186. Epub 2018 Feb 28.

Abstract

MicroRNAs (miRNAs) are small non-coding RNAs that play important roles in a variety of biological processes. Dysregulation of miRNAs is tightly associated with the malignancy of cancers. Aberrant expression of miR-378 has been observed in human cancers; however, the function of miR-378 in osteosarcoma (OS) remains largely unknown. Here, we showed that miR-378 was highly expressed in human OS tissues and cell lines. Overexpression of miR-378 significantly promoted the cell proliferation of OS cells. Molecular studies identified Kruppel-like factor-9 (KLF9) as a functional downstream target of miR-378. MiR-378 directly bound to the mRNA 3'-UTR region of KLF9 and suppressed the expression of KLF9. Highly expressed KLF9 reversed the promoting effect of miR-378 on the proliferation of OS cells. The expression level of miR-378 was negatively correlated with that of KLF9 in OS tissues. Collectively, our results demonstrated the molecular interaction between miR-378 and KLF9, indicating the therapeutic potential of miR-378 for OS.

Keywords: KLF9; cell proliferation; expression génique; gene expression; miR-378; osteosarcoma; ostéosarcome; prolifération cellulaire.

MeSH terms

  • Bone Neoplasms / genetics
  • Bone Neoplasms / metabolism*
  • Bone Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Proliferation*
  • Down-Regulation*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Kruppel-Like Transcription Factors / biosynthesis*
  • Kruppel-Like Transcription Factors / genetics
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • Osteosarcoma / genetics
  • Osteosarcoma / metabolism*
  • Osteosarcoma / pathology
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism*

Substances

  • KLF9 protein, human
  • Kruppel-Like Transcription Factors
  • MIRN378 microRNA, human
  • MicroRNAs
  • Neoplasm Proteins
  • RNA, Neoplasm