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.
Oral Oncol
; 50(5): 448-56, 2014 May.
Article
in En
| MEDLINE
| ID: mdl-24565984
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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Carcinoma, Squamous Cell
/
Signal Transduction
/
Down-Regulation
/
Rho GTP-Binding Proteins
/
MicroRNAs
/
Head and Neck Neoplasms
Limits:
Humans
Language:
En
Journal:
Oral Oncol
Journal subject:
NEOPLASIAS
Year:
2014
Document type:
Article