Elevated microRNA-145 inhibits the development of oral squamous cell carcinoma through inactivating ERK/MAPK signaling pathway by down-regulating HOXA1

Biosci Rep. 2019 Jun 25;39(6):BSR20182214. doi: 10.1042/BSR20182214. Print 2019 Jun 28.

Abstract

Background: Oral cancer is one of the most frequent solid cancers worldwide, and oral squamous cell carcinoma (OSCC) constitutes approximately 90% of oral cancers. The discovery of reliable prognostic indicators would be a potential strategy for OSCC treatment. In the present study, we aim to explore the underlying mechanism by which microRNA-145 (miR-145) affected OSCC. Methods: Forty-eight patients diagnosed with OSCC were enrolled to obtain the OSCC tissues and adjacent normal tissues. The targeting relationship between miR-145 and Homeobox A1 (HOXA1) was verified. In order to assess the effects of miR-145 in OSCC and the detailed regulatory mechanism, the SCC-9 cell line was adopted, in which expression of miR-145 and HOXA1 were altered by transfection. Then, a series of in vitro and in vivo experiments were performed to evaluate the cell viability, migration, invasion, and tumor growth. Results: miR-145 was poorly expressed and HOXA1 was highly expressed in OSCC. HOXA1 was verified as a target of miR-145 to mediate the activation of the extracellular signal-regulated kinase/mitogen activated protein kinase (ERK/MAPK) signaling pathway. In the circumstance of miR-145 elevation or HOXA1 depletion, the SCC-9 cell line manifested with inhibited cell viability, invasion, and migration in vitro, coupled with reduced tumor growth in vivo, with a decreased expression of ERK/MAPK signaling pathway-related genes/proteins. Conclusion: These findings suggested that miR-145 can inhibit HOXA1 to inactivate the ERK/MAPK signaling pathway, thereby suppressing OSCC cell proliferation, migration, and invasion to further inhibit the development of OSCC, highlighting a novel therapeutic target for the OSCC treatment.

Keywords: Extracellular-signal-regulated kinase/mitogen activated protein kinase; Homeobox A1; MicroRNA-145; Oral squamous cell carcinoma.

Publication types

  • Retracted Publication

MeSH terms

  • Adult
  • Aged
  • Animals
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Cell Survival / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Heterografts
  • Homeodomain Proteins / genetics*
  • Humans
  • Lymphatic Metastasis
  • MAP Kinase Signaling System / genetics
  • Male
  • Mice
  • MicroRNAs / genetics*
  • Middle Aged
  • Mouth Neoplasms / genetics*
  • Mouth Neoplasms / pathology
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Transcription Factors / genetics*

Substances

  • Homeodomain Proteins
  • MIRN145 microRNA, human
  • MicroRNAs
  • Transcription Factors
  • homeobox A1 protein