MicroRNA-9 promotes tumor metastasis via repressing E-cadherin in esophageal squamous cell carcinoma.
MicroRNAs (miRNAs) play a critical role in development and progression of cancers. Deregulation of MicroRNA-9 (miR-9) has been documented in many types of cancers but their role in the development of esophageal squamous cell carcinoma (ESCC) has not been studied. This study aimed to investigate the effect of miR-9 in esophageal cancer metastasis. The up-regulation of miR-9 was frequently detected in primary ESCC tumor tissue, which was significantly associated with clinical progression (P = 0.022), lymph node metastasis (P = 0.007) and poor overall survival (P < 0.001). Functional study demonstrated that miR-9 promoted cell migration and tumor metastasis, which were effectively inhibited when expression of miR-9 was silenced. Moreover, we demonstrated that miR-9 interacted with the 3'-untranslated region of E-cadherin and down-regulated its expression, which induced β-catenin nuclear translocation and subsequently up-regulated c-myc and CD44 expression. In addition, miR-9 induced epithelial-mesenchymal transition (EMT) in ESCC, a key event in tumor metastasis. Taken together, our study demonstrates that miR-9 plays an important role in ESCC metastasis by activating β-catenin pathway and inducing EMT via targeting E-cadherin. Our study also suggests miR-9 can be served as a new independent prognostic marker and/or as a novel potential therapeutic target for ESCC.
State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China.
Ye
Y
Song
Vascular Biology Research Institute, Guangdong Pharmaceutical University, Guangzhou, 510060, China.
Jiangchao
J
Li
State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China.
Yinghui
Y
Zhu
State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China.
Yongdong
Y
Dai
State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China.
Tingting
T
Zeng
State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China.
Lulu
L
Liu
State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China.
Jianbiao
J
Li
State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China.
Hongbo
H
Wang
Department of Clinical Oncology, the First Affiliated Hospital, Zhengzhou University, Zhengzhou, 510060, China.
Yanru
Y
Qin
State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China.
Musheng
M
Zeng
State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China. Department of Clinical Oncology, The University of Hong Kong, Hong Kong, China.
Xin-Yuan
XY
Guan
State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China.
Yan
Y
Li
D020413:3' Untranslated Regions; D021581:Active Transport, Cell Nucleus; D015703:Antigens, CD; D015820:Cadherins / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D018450:Disease Progression; D015536:Down-Regulation; D004938:Esophageal Neoplasms / Q000378:metabolism*; D000077277:Esophageal Squamous Cell Carcinoma; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D017403:In Situ Hybridization; D035683:MicroRNAs / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D009362:Neoplasm Metastasis; D011379:Prognosis; D016016:Proportional Hazards Models; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D016896:Treatment Outcome; D051176:beta Catenin / Q000378:metabolism
D020413:3' Untranslated Regions; D015703:Antigens, CD; C497483:CD44 protein, human; C513384:CDH1 protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; D018960:Hyaluronan Receptors; C541874:MIRN92 microRNA, human; C489427:MYC protein, human; D035683:MicroRNAs; D016271:Proto-Oncogene Proteins c-myc; D051176:beta Catenin