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KNTC1 knockdown inhibits the proliferation and migration of osteosarcoma cells by MCM2

Lei Zhong1, Yuanwei Dong1, Shuqin Liu2

  • 1Department of Orthopedics, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China.

Molecular Carcinogenesis
|May 31, 2024
PubMed

Insights

Kinetochore associated protein 1 (KNTC1) is overexpressed in osteosarcoma (OS) and drives tumor progression. Downregulating KNTC1 inhibits OS cell proliferation and migration by reducing minichromosome maintenance 2 (MCM2) expression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Osteosarcoma (OS) is a primary malignant bone tumor requiring further investigation into its molecular mechanisms.
  • Understanding the progression of OS is crucial for developing effective therapeutic strategies.

Purpose of the Study:

  • To investigate the role of kinetochore associated protein 1 (KNTC1) in osteosarcoma (OS) progression.
  • To identify downstream molecules regulated by KNTC1 and their impact on OS development.

Main Methods:

  • Immunohistochemistry, qPCR, and Western blot were used to detect KNTC1 and minichromosome maintenance 2 (MCM2) expression.
  • In vitro cell models (gene knockdown/overexpression) and in vivo xenograft models were employed to assess functional effects.
  • Bioinformatics analysis was performed to identify downstream targets and analyze MCM2 expression across cancers.

Main Results:

  • KNTC1 was found to be overexpressed in OS tissues and correlated with poorer overall survival.
  • KNTC1 knockdown suppressed OS cell proliferation, migration, induced apoptosis, and cell cycle arrest at G2 phase.
  • Downregulation of KNTC1 inhibited xenograft tumor formation, and MCM2 was identified as a key downstream target whose upregulation promotes OS progression.

Conclusions:

  • KNTC1 is oncogenic in OS, promoting tumor progression by upregulating MCM2.
  • Targeting KNTC1 may represent a potential therapeutic strategy for osteosarcoma.
Keywords:
KNTC1MCM2osteosarcomaproliferation

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