Downregulation of miR-377 Promotes Oral Squamous Cell Carcinoma Growth and Migration by Targeting HDAC9

Cancer Invest. 2017 Mar 16;35(3):152-162. doi: 10.1080/07357907.2017.1286669. Epub 2017 Mar 7.

Abstract

microRNAs are the post-transcriptional regulators implicated in the initiation and progression of various cancer types, including oral squamous cell carcinoma (OSCC). Here, we investigated the role of miR-377 in OSCC tumorigenesis. miR-377 expression was reduced in OSCC samples and cell line (UPCI-SCC-116), and was associated with patient survival. In vitro restoration of miR-377 repressed cell growth, induced apoptosis, and reduced cell migration. We identified HDAC9 as a target of miR-377 and found miR-377 to regulate HDAC9 and its pro-apoptotic target, NR4A1/Nur77. Our findings show that miR-377 targets HDAC9 pathway in OSCC, suggesting that miR-377-HDAC9 axis may provide a novel therapeutic target for OSCC therapy.

Keywords: Histone deacetylase 9; Oral squamous cell carcinoma; microRNA-377.

MeSH terms

  • 3' Untranslated Regions
  • Apoptosis
  • Base Sequence
  • Binding Sites
  • Carcinoma, Squamous Cell / enzymology
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Down-Regulation
  • Enzyme Repression
  • Gene Expression Regulation, Neoplastic*
  • Histone Deacetylases
  • Humans
  • Kaplan-Meier Estimate
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Mouth Neoplasms / enzymology
  • Mouth Neoplasms / genetics*
  • Mouth Neoplasms / mortality
  • Mouth Neoplasms / pathology
  • Nuclear Receptor Subfamily 4, Group A, Member 1 / genetics
  • Nuclear Receptor Subfamily 4, Group A, Member 1 / metabolism
  • RNA Interference*
  • Repressor Proteins

Substances

  • 3' Untranslated Regions
  • MIRN377 microRNA, human
  • MicroRNAs
  • NR4A1 protein, human
  • Nuclear Receptor Subfamily 4, Group A, Member 1
  • Repressor Proteins
  • HDAC9 protein, human
  • Histone Deacetylases