MicoRNA-451 is a novel tumor suppressor via targeting c-myc in head and neck squamous cell carcinomas.
OBJECTIVE
Head and neck squamous cell carcinoma (HNSCC) represents as a common malignancy with increasing incidence in the worldwide. The fact of its poor survival rate urgently requires developing efficient predictive biomarkers for clinical use. MicroRNAs (miRNAs) recently represent as a novel direction for early diagnosis and prognosis prediction in HNSCC therapy. In this study, we comprehensively investigated the function and putative target of miRNA-451 in vitro.


METHODS
The expression of miRNA-451 was detected in HNSCC tissues and cell lines by real-time PCR. Forced expression or inhibition of miRNA-451 was done by transient transfection of mimics or inhibitor of miRNA-451 into indicated cells, respectively. Cell proliferation was evaluated by cell counting and crystal staining. Afterwards, we perform western blot to verify the expression of the miRNA-451 predicted target, c-myc, after miRNA-451 was overexpressed.


RESULTS
We showed that miRNA-451 was downregulated in paired HNSCC tissues as well as in cell lines. And overexpression of miRNA-451 in cells with low endogenous expression of miRNA-451 accelerated proliferation. To the contrast, knockdown of miRNA-451 in cells with high levels of miRNA-451 significantly reduced cell growth rate. Furthermore, we used bioinformatics and cellular methods to predict and prove that c-myc was targeted by miRNA-451, since forced expression of miRNA-451 leaded to decreased c-myc protein expression in HNSCC cells.


CONCLUSIONS
Our findings identify miRNA-451 as a potential biomarker and suggest a key role of miRNA-451-c-myc pathway in HNSCC cell transformation, which could represent a novel therapeutic strategy in HNSCC treatment.
Huimin
H
Wang
Guozheng
G
Zhang
Zhiyan
Z
Wu
Baocai
B
Lu
Dongjie
D
Yuan
Xiao
X
Li
Department of Otolaryngology, Head and Neck Surgery, The First Affiliated Hospital of Xinxiang Medical College, Xinxiang 453100, Henan Province, China.
Zhenmin
Z
Lu
D001665:Binding Sites; D014408:Biomarkers, Tumor; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D002460:Cell Line; D049109:Cell Proliferation / Q000235:genetics; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D006801:Humans; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc / Q000737:chemistry / Q000235:genetics*; D034622:RNA Interference; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D000077195:Squamous Cell Carcinoma of Head and Neck
D014408:Biomarkers, Tumor; C531201:MIRN451 microRNA, human; D035683:MicroRNAs; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger