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Oral Oncol. 2014 May;50(5):448-56. doi: 10.1016/j.oraloncology.2014.01.014. Epub 2014 Feb 22.

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.

Author information

1
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.
2
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University, Wexner Medical Center, Columbus, OH, USA.
3
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.

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.

CONCLUSION:

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.

KEYWORDS:

Erk(1/2); FAK; Head and neck cancer; RhoC; Src; miR-138

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