miR-224 promotion of cell migration and invasion by targeting Homeobox D 10 gene in human hepatocellular carcinoma.
OBJECTIVE
MicroRNAs (miRNAs) are small noncoding RNA molecules that control target gene expression and are implicated in the regulation of diverse cellular pathways. In our previous research, we have demonstrated that miR-224 was overexpressed in liver cancer cells and tissues, which was an important factor in the regulation of cell migration and invasion. This study aimed to further explore the regulatory mechanism of miR-224 in the migration and invasion in liver cancer cells.


METHODS
A luciferase reporter assay was used to confirm that the HOXD10 gene was a direct target of miR-224. Quantitative reverse transcriptase-polymerase chain reaction, Western blotting, Transwell migration, and Matrigel invasion assays were performed to clarify the molecular mechanism of miR-224 in the regulation of cell migration and invasion in human hepatocellular carcinoma (HCC).


RESULTS
(i) The expression of miR-224 was strongly upregulated in MHHC97H and MHCC97L cells, and its expression level was significantly associated with cell invasive potential. (ii) The HOXD10 gene was confirmed to be a direct target of miR-224. Compared with normal liver tissues and cells, HOXD10 had lower expression in HCC tissues and cells and inversely regulated HCC cell invasion. (iii) miR-224 promoted expression of the tumor invasion-associated proteins p-PAK4 and MMP-9 by directly targeting HOXD10.


CONCLUSIONS
Our findings suggest a previously undescribed regulatory pathway in which the miR-224/HOXD10/p-PAK4/MMP-9 signaling pathway contributes to the regulation of cell migration and invasion and provides a new biotarget for HCC treatment.
Experimental Center of Basic Medicine, College of Basic Medical Science, Third Military Medical University, Chongqing, China.
Qiong
Q
Li
Chenchen
C
Ding
Chuan
C
Chen
Zhimin
Z
Zhang
He
H
Xiao
Fei
F
Xie
Lin
L
Lei
Yuanyuan
Y
Chen
Bijing
B
Mao
Mei
M
Jiang
Jian
J
Li
Dong
D
Wang
Ge
G
Wang
D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D015870:Gene Expression / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D018398:Homeodomain Proteins / Q000502:physiology*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D035683:MicroRNAs / Q000502:physiology*; D009361:Neoplasm Invasiveness / Q000235:genetics; D014157:Transcription Factors / Q000502:physiology*; D054462:p21-Activated Kinases / Q000378:metabolism
D018398:Homeodomain Proteins; C546140:MIRN224 microRNA, human; D035683:MicroRNAs; D014157:Transcription Factors; C072064:HOXD10 protein, human; C116367:PAK4 protein, human; D054462:p21-Activated Kinases; D020780:Matrix Metalloproteinase 9
HOXD10; human hepatocellular carcinoma (HCC); invasion; miR-224; migration