MicroRNA-144 suppresses osteosarcoma growth and metastasis by targeting ROCK1 and ROCK2

Oncotarget. 2015 Apr 30;6(12):10297-308. doi: 10.18632/oncotarget.3305.

Abstract

Osteosarcoma (OS) is the most common primary tumor of bone. MicroRNAs (miRNAs) are a class of endogenously expressed small non-coding RNAs that are strongly implicated in cancerous processes. However, our current understanding of the biological role of miRNAs in OS remains incomplete. In the present study, miR-144 was markedly downregulated in OS cell lines and clinical specimens. Low-level expression of miR-144 was significantly associated with distant metastasis and poor prognosis. Functional studies demonstrated that ectopic expression of miR-144 suppresses tumor cell proliferation and metastasis in vitro as well as in vivo. Furthermore, we identified Rho-associated kinases 1 and 2 (ROCK1 and ROCK2) as direct targets for miR-144 binding, resulting in suppression of their expression. Exogenous expression of ROCK1 or ROCK2 in 143B-miR-144 cells partially restored miR-144-inhibited cell proliferation and invasion. In clinical OS specimens, ROCK1 and ROCK2 levels were elevated, relative to that in paired normal bone tissues, and inversely correlated with miR-144 expression. Taken together, miR-144 suppresses OS progression by directly downregulating ROCK1 and ROCK2 expression, and may be a promising therapeutic target for OS.

Keywords: ROCK1; ROCK2; metastasis; miR-144; osteosarcoma.

MeSH terms

  • Animals
  • Bone Neoplasms / enzymology
  • Bone Neoplasms / genetics*
  • Bone Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Proliferation / physiology
  • Disease Progression
  • Down-Regulation
  • Heterografts
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Osteosarcoma / enzymology
  • Osteosarcoma / genetics*
  • Osteosarcoma / pathology
  • Transfection
  • rho-Associated Kinases / genetics
  • rho-Associated Kinases / metabolism*

Substances

  • MIRN144 microRNA, human
  • MicroRNAs
  • ROCK1 protein, human
  • ROCK2 protein, human
  • rho-Associated Kinases