miR-373-3p Targets DKK1 to Promote EMT-Induced Metastasis via the Wnt/β-Catenin Pathway in Tongue Squamous Cell Carcinoma.
MicroRNAs (miRNAs) regulate gene expression and at the same time mediate tumorigenesis. miR-373-3p has diverse effects in tumors, but its role in tongue squamous cell carcinoma (TSCC) remains unknown. The purpose of this study is to determine the function of miR-373-3p in the progression of TSCC. Our results brought to light that miR-373-3p is markedly upregulated in clinical TSCC tissues compared with paired adjacent normal tissues and has significant correlation with a more aggressive TSCC phenotype in patients. Gain-of-function and loss-of-function studies revealed that ectopic miR-373-3p overexpression promoted the metastasis of TSCC cells. Notably, Wnt/β-catenin signaling was hyperactivated in TSCC cells overexpressing miR-373-3p, and this pathway was responsible for the epithelial-mesenchymal transition (EMT) induced by miR-373-3p. Furthermore, miR-373-3p directly targeted and suppressed Dickkopf-1 (DKK1), a negative regulator of the Wnt/β-catenin signaling cascade. These results demonstrate that, by directly targeting DKK1, miR-373-3p constitutively activated Wnt/β-catenin signaling, thus promoting the EMT-induced metastasis of TSCC. Taken together, our findings reveal a new regulatory mechanism for miR-373-3p and suggest that miR-373-3p might be a potential target in TSCC therapy.
Department of Oral and Maxillofacial Surgery, Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055, China; Department of Stomatology, Shenzhen People's Hospital, Second Clinical Medical School of Jinan University, Shenzhen, Guangdong 518020, China.
Junquan
0000-0002-1128-2555
J
Weng
Department of Oral and Maxillofacial Surgery, Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055, China; Department of Stomatology, Pingshan New District People's Hospital of Shenzhen, Shenzhen, Guangdong 518118, China.
Hui
H
Zhang
Department of Oral and Maxillofacial Surgery, Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055, China; Guangdong Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
Cheng
C
Wang
Department of Oral and Maxillofacial Surgery, Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055, China; Guangdong Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
Jianfeng
J
Liang
Department of Oral and Maxillofacial Surgery, Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055, China; Guangdong Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
Guanhui
G
Chen
Department of Oral and Maxillofacial Surgery, Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055, China; Guangdong Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
Wenqing
W
Li
Department of Oral and Maxillofacial Surgery, Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055, China; Guangdong Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
Haikuo
H
Tang
Department of Oral and Maxillofacial Surgery, Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510055, China; Guangdong Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
Jinsong
0000-0003-2699-0543
J
Hou
D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D009362:Neoplasm Metastasis; D014062:Tongue Neoplasms / Q000235:genetics* / Q000473:pathology; D060449:Wnt Signaling Pathway / Q000235:genetics
C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; C527114:MIRN373 microRNA, human; D035683:MicroRNAs