OTX1 exerts an oncogenic role and is negatively regulated by miR129-5p in laryngeal squamous cell carcinoma

BMC Cancer. 2020 Aug 24;20(1):794. doi: 10.1186/s12885-020-07279-1.

Abstract

Background: Orthodenticle homeobox 1 (OTX1) is a transcription factor that plays an important role in various human cancers. However, the function of OTX1 in laryngeal squamous cell carcinoma (LSCC) is largely unknown. We aimed to explore the roles of OTX1 in LSCC and its possible molecular mechanism.

Methods: The expression levels of OTX1 were assessed in LSCC cell lines and tissue samples. We further examined the effect of OTX1 on LSCC progression. The upstream regulator of OTX1 was identified using a computer algorithm and confirmed experimentally.

Results: OTX1 was highly expressed in 70.7% (70/99) of LSCC tissue samples. The OTX1 expression in LSCC was significantly correlated with lymph node metastasis. High OTX1 expression in patients with LSCC was correlated with poor prognosis. Knockdown of OTX1 inhibited proliferation, colony formation, migration and invasion in LSCC cells. Knockdown of OTX1 inhibited tumor growth in a xenograft mouse model. Mechanistically, OTX1 might act as a direct target of miR-129-5p. OTX1 enhanced tumorigenicity and tumor growth both in vitro and in vivo.

Conclusions: Our findings support that OTX1 is an oncogene in LSCC tumorigenesis and progression. Furthermore, OTX1 is a direct target of miR-129-5p in LSCC cells. Taken together, OTX1 is a promising diagnostic and therapeutic marker for LSCC.

Keywords: Laryngeal squamous cell carcinoma; MiR-129-5p; Orthodenticle homeobox 1; Prognosis; Tumor progression.

MeSH terms

  • Animals
  • Biomarkers, Tumor / genetics*
  • Carcinogenesis / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • Kaplan-Meier Estimate
  • Laryngeal Neoplasms / diagnosis
  • Laryngeal Neoplasms / genetics*
  • Laryngeal Neoplasms / mortality
  • Laryngeal Neoplasms / surgery
  • Laryngectomy
  • Larynx / pathology
  • Larynx / surgery
  • Male
  • Mice
  • MicroRNAs / metabolism*
  • Middle Aged
  • Otx Transcription Factors / genetics*
  • Retrospective Studies
  • Squamous Cell Carcinoma of Head and Neck / diagnosis
  • Squamous Cell Carcinoma of Head and Neck / genetics*
  • Squamous Cell Carcinoma of Head and Neck / mortality
  • Squamous Cell Carcinoma of Head and Neck / surgery
  • Xenograft Model Antitumor Assays

Substances

  • Biomarkers, Tumor
  • MicroRNAs
  • Mirn129 microRNA, human
  • OTX1 protein, human
  • Otx Transcription Factors