title: Down regulation of RhoC by microRNA-138 results in de-activation of FAK, Src and Erk1/2 signaling pathway in head and neck squamous cell carcinoma.
abstract: OBJECTIVE
  RhoC a pro-metastatic oncogene is constitutively active in many head and neck squamous cell carcinomas. MicroRNA-138 which possesses a documented tumor suppressor function can bind to the 3'UTR of RhoC mRNA and inhibit its activity. We hypothesize that miR-138 can inhibit the function of RhoC and consequently the activation of downstream target molecules involve in the signaling cascade. For this reason we investigated the role of miR-138 in HNSCC.
  
  
  METHODS
  In vitro studies were carried out to evaluate the role of miR-138 in HNSCC cell lines and in primary tumors obtained from HNSCC patients. Real time RT-PCR, Western blot, cell motility, invasion and colony formation assays were performed according to standard procedures.
  
  
  RESULTS
  Data obtained by G-LISA and real time PCR shows an inverse correlation between RhoC expression and miR-138 in HNSCC cell lines. Additionally, we obtained a similar pattern of RhoC and miR-138 expression in primary tumors from HNSCC patients. Over expression of miR-138 in HNSCC lines showed down regulation of RhoC, as well as a decrease in cell motility, invasion colony and stress fiber formation. Furthermore, a significant down regulation was observed for FAK, Src and Erk(1/2) upon miR-138 overexpression.
  
  
  CONCLUSIONS
  These findings strongly suggest that the inhibition of RhoC can be achieved by over expressing miR-138, which further attenuates the downstream signaling cascade leading to cancer progression and survival. Moreover, this study for the first time shows that down regulation of FAK, Src and Erk(1/2) by miR-138 overexpression is due to inhibition of RhoC in HNSCC.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, The Ohio State University, Wexner Medical Center, Columbus, OH, USA; Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University, Wexner Medical Center, Columbus, OH, USA. Electronic address: Mozaffarul.Islam@osumc.edu.
authors.forename: Mozaffarul
authors.initials: M
authors.lastname: Islam
authors.affiliation: Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University, Wexner Medical Center, Columbus, OH, USA.
authors.forename: Jharna
authors.initials: J
authors.lastname: Datta
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, The Ohio State University, Wexner Medical Center, Columbus, OH, USA; Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University, Wexner Medical Center, Columbus, OH, USA.
authors.forename: James C
authors.initials: JC
authors.lastname: Lang
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, The Ohio State University, Wexner Medical Center, Columbus, OH, USA; Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University, Wexner Medical Center, Columbus, OH, USA.
authors.forename: Theodoros N
authors.initials: TN
authors.lastname: Teknos
mesh_terms: D020413:3' Untranslated Regions; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D015536:Down-Regulation; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D020935:MAP Kinase Signaling System; D035683:MicroRNAs / Q000502:physiology*; D016392:Proto-Oncogene Proteins pp60(c-src); D015398:Signal Transduction; D020741:rho GTP-Binding Proteins / Q000378:metabolism*; D000075024:rhoC GTP-Binding Protein
chemical_list: D020413:3' Untranslated Regions; C546110:MIRN138 microRNA, human; D035683:MicroRNAs; D051416:Focal Adhesion Protein-Tyrosine Kinases; D016392:Proto-Oncogene Proteins pp60(c-src); C066690:RHOC protein, human; D020741:rho GTP-Binding Proteins; D000075024:rhoC GTP-Binding Protein
keywords: Erk(1/2); FAK; Head and neck cancer; RhoC; Src; miR-138