title: miR-433 inhibits oral squamous cell carcinoma (OSCC) cell growth and metastasis by targeting HDAC6.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Stomatology, The Fourth College, Harbin Medical University, China.
authors.forename: Xiao-chun
authors.initials: XC
authors.lastname: Wang
authors.affiliation: Department of Stomatology, The Fourth College, Harbin Medical University, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Stomatology, The Fourth College, Harbin Medical University, China.
authors.forename: Pei-song
authors.initials: PS
authors.lastname: Meng
authors.affiliation: Department of Stomatology, The Fourth College, Harbin Medical University, China.
authors.forename: Jia-long
authors.initials: JL
authors.lastname: Han
authors.affiliation: Department of Stomatology, The Fourth College, Harbin Medical University, China.
authors.forename: Hai-yan
authors.initials: HY
authors.lastname: Yu
authors.affiliation: Department of Stomatology, The Fourth College, Harbin Medical University, China. Electronic address: biliangjia1001@126.com.
authors.forename: Liang-jia
authors.initials: LJ
authors.lastname: Bi
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; C403126:MYLIP protein, human; D044767:Ubiquitin-Protein Ligases; C433811:HDAC6 protein, human; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases
keywords: HDAC6; HSC2; Oral squamous cell carcinoma (OSCC); SAS; miR-433