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Downregulation of NKD1 in human osteosarcoma and its clinical significance

Xiang Chen1, Ping Xu2, Jianwei Zhu1

  • 1Department of Orthopedics, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China.

Molecular Medicine Reports
|November 9, 2017
PubMed

Insights

Naked cuticle homolog 1 (NKD1) is downregulated in osteosarcoma, correlating with metastasis and advanced stage. Restoring NKD1 inhibits cancer cell growth and migration by suppressing the Wnt/β‑catenin pathway, suggesting NKD1 as a potential therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Naked cuticle homolog 1 (NKD1) negatively regulates the Wnt/β‑catenin pathway and is expressed in normal tissues.
  • Limited data exists on NKD1 expression and its role in human osteosarcoma.

Purpose of the Study:

  • To investigate NKD1 expression levels in osteosarcoma.
  • To determine the clinicopathological significance of NKD1 in osteosarcoma.
  • To explore the functional role of NKD1 in osteosarcoma cell proliferation and migration.

Main Methods:

  • Western blotting and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to measure NKD1 mRNA and protein expression.
  • NKD1 was overexpressed in MG63 osteosarcoma cells using adenovirus transfection.
  • Expression of β‑catenin, cyclin D1, and MMP‑9 was assessed following NKD1 upregulation.

Main Results:

  • NKD1 expression was significantly lower in osteosarcoma tissues than in normal bone.
  • Reduced NKD1 levels correlated with lung metastasis and higher Enneking stage.
  • Overexpression of NKD1 in MG63 cells inhibited cell proliferation and migration.
  • Upregulated NKD1 suppressed β‑catenin, cyclin D1, and MMP‑9 protein expression.

Conclusions:

  • Downregulation of NKD1 is associated with osteosarcoma progression, metastasis, and staging.
  • NKD1 inactivation may promote osteosarcoma via Wnt/β‑catenin pathway activation.
  • NKD1 represents a potential prognostic biomarker and therapeutic target for osteosarcoma.

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