MicroRNA-9 promotes tumor metastasis via repressing E-cadherin in esophageal squamous cell carcinoma
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Ye Song1, Jiangchao Li2, Yinghui Zhu1, Yongdong Dai1, Tingting Zeng1, Lulu Liu1, Jianbiao Li1, Hongbo Wang1, Yanru Qin3, Musheng Zeng1, Xin-Yuan Guan1,4, Yan Li1
1State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China
2Vascular Biology Research Institute, Guangdong Pharmaceutical University, Guangzhou, 510060, China
3Department of Clinical Oncology, the First Affiliated Hospital, Zhengzhou University, Zhengzhou, 510060, China
4Department of Clinical Oncology, The University of Hong Kong, Hong Kong, China
Yan Li, e-mail: firstname.lastname@example.org
XY Guan, e-mail: email@example.com
Keywords: miR-9, ESCC, E-cadherin, metastasis, β-catenin
Received: August 11, 2014 Accepted: October 09, 2014 Published: October 31, 2014
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.
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