miR-433 inhibits oral squamous cell carcinoma (OSCC) cell growth and metastasis by targeting HDAC6

Oral Oncol. 2015 Jul;51(7):674-82. doi: 10.1016/j.oraloncology.2015.04.010. Epub 2015 May 8.

Abstract

Objectives: The aim of this study was to determine expression levels of miR-433 in oral squamous cell carcinomas (OSCCs) and adjacent normal tissues, and explore its biological functions in OSCCs.

Methods: miR-433 level in oral squamous cell carcinomas (OSCCs) and adjacent normal tissues was tested by real-time qPCR. The effect of miR-433 on cell growth was detected by MTT and colony formation assays. The tumorigenicity of miR-433 transfected OSCCs was evaluated in nude mice model. Transwell and wound healing assays were performed to detect the effect of miR-433 on OSCCs cell invasion and migration. Luciferase reporter gene assays were performed to identify the interaction between miR-433 and 3'UTR of HDAC6 mRNA. The protein level of HDAC6, BCL2, CCNE1, MMP1 and MMP9 was determined by Western blotting. Immunohistochemistry analysis was performed to detect the expression of HDAC6 in oral squamous cell carcinomas (OSCCs) and adjacent normal tissues.

Results: We found that miR-433 was frequently down-regulated in OSCCs compared with adjacent normal tissues. Restoring miR-433 expression in OSCC cells dramatically suppressed cells growth, invasion and migration. Importantly, our data showed that miR-433 downregulated the expression of HDAC6 through directly targeting its 3'UTR.

Conclusion: Our data suggest that miR-433 exerts its tumor suppressor function by targeting HDAC6, leading to the inhibition of OSCC cell growth, invasion and migration, which suggest that miR-433 may be potential target for diagnostic and therapeutic applications in OSCC.

Keywords: HDAC6; HSC2; Oral squamous cell carcinoma (OSCC); SAS; miR-433.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Disease Models, Animal
  • Female
  • Histone Deacetylase 6
  • Histone Deacetylases / metabolism*
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Middle Aged
  • Mouth Neoplasms / genetics
  • Mouth Neoplasms / metabolism*
  • Mouth Neoplasms / pathology
  • RNA, Messenger / metabolism
  • Real-Time Polymerase Chain Reaction
  • Ubiquitin-Protein Ligases / metabolism*

Substances

  • RNA, Messenger
  • MYLIP protein, human
  • Ubiquitin-Protein Ligases
  • HDAC6 protein, human
  • Histone Deacetylase 6
  • Histone Deacetylases