miR-125a Promotes the Progression of Giant Cell Tumors of Bone by Stimulating IL-17A and β-Catenin Expression

  • Mol Ther Nucleic Acids. 2018 Dec 7;13:493-502. doi: 10.1016/j.omtn.2018.09.021.
Hua Jin  1 ,  Dian-Wei Li  2 ,  Shu-Nan Wang  3 ,  Song Luo  4 ,  Qing Li  5 ,  Ping Huang  5 ,  Jian-Min Wang  6 ,  Meng Xu  7 ,  Cheng-Xiong Xu  8
Affiliations
  • 1. Department of Thoracic Surgery, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, China.
  • 2. Department of Orthopaedics, The SouthWest Hospital, Third Military Medical University, Chongqing 400038, China.
  • 3. Department of Radiology, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, China.
  • 4. Department of Orthopaedics, The General Hospital of Chinese People's Liberation Army, Beijing 100853, China.
  • 5. Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, China.
  • 6. State Key Laboratory of Trauma, Burn and Combined Injury, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, China.
  • 7. Department of Orthopaedics, The General Hospital of Chinese People's Liberation Army, Beijing 100853, China. Electronic address: [email protected].
  • 8. Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, China. Electronic address: [email protected].
PMID: 30388623 DOI: 10.1016/j.omtn.2018.09.021
Abstract

Giant cell tumors of bone (GCTBs) exhibit high recurrence and aggressive bone lytic behavior; but, the mechanism of GCTB progression is largely unknown. In GCTB, we detected abundant levels of miR-125a, which were associated with tumor extension, grade, and recurrence. miR-125a stimulates stromal cell tumorigenicity and growth in vivo by promoting the expression of interleukin-17A (IL-17A) and β-catenin. In contrast, inhibition of miR-125a suppressed stromal cell tumorigenicity and growth. Then, we found that miR-125a stimulates IL-17A by targeting TET2 and Foxp3, and it stimulates β-catenin expression by targeting APC and GSK3β in stromal cells. Furthermore, we identified that IL-17A stimulates miR-125a by activating nuclear factor κB (NF-κB) signaling in stromal cells. Finally, our data show that simultaneous inhibition of IL-17A signaling and miR-125a more significantly inhibits stromal cell growth than miR-125a inhibition alone. miR-125a stimulates the progression of GCTB, and it might represent a useful candidate marker for progression. Simultaneously blocking miR-125a and IL-17A might represent a new therapeutic strategy for GCTB.

Keywords
GCTB; IL-17A; miR-125a; recurrence; β-catenin signaling.
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