Ino80 promotes cervical cancer tumorigenesis by activating Nanog expression

Oncotarget. 2016 Nov 1;7(44):72250-72262. doi: 10.18632/oncotarget.12667.

Abstract

Ino80 ATPase is an integral component of the INO80 ATP-dependent chromatin-remodeling complex, which regulates transcription, DNA repair and replication. We found that Ino80 was highly expressed in cervical cancer cell lines and tumor samples. Ino80 knockdown inhibited cervical cancer cell proliferation, induced G0/G1 phase cell cycle arrest in vitro and suppressed tumor growth in vivo. However, Ino80 knockdown did not affect cell apoptosis, migration or invasion in vitro. Ino80 overexpression promoted proliferation in the H8 immortalized cervical epithelial cell line, which has low endogenous Ino80 expression as compared to cervical cancer cell lines. Ino80 bound to the Nanog transcription start site (TSS) and enhanced its expression in cervical cancer cells. Nanog overexpression in Ino80 knockdown cell lines promoted cell proliferation. This study demonstrated for the first time that Ino80 was upregulated in cervical cancer and promoted cell proliferation and tumorigenesis. Our findings suggest that Ino80 may be a potential therapeutic target for the treatment of cervical cancer.

Keywords: Ino80; cervical cancer; proliferation; tumorigenesis; Nanog.

MeSH terms

  • ATPases Associated with Diverse Cellular Activities
  • Animals
  • Apoptosis
  • Carcinogenesis / genetics*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cervix Uteri / pathology
  • DNA Helicases / metabolism*
  • DNA-Binding Proteins
  • Epigenesis, Genetic
  • Female
  • Fluorescent Antibody Technique
  • G1 Phase Cell Cycle Checkpoints
  • Gene Expression Regulation, Neoplastic*
  • Gene Knockdown Techniques
  • Humans
  • Mice
  • Mice, Nude
  • Nanog Homeobox Protein / genetics*
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Transcription Initiation Site
  • Up-Regulation
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / pathology
  • Xenograft Model Antitumor Assays

Substances

  • DNA-Binding Proteins
  • NANOG protein, human
  • Nanog Homeobox Protein
  • RNA, Small Interfering
  • ATPases Associated with Diverse Cellular Activities
  • DNA Helicases
  • INO80 protein, human