The SOX17/miR-371-5p/SOX2 axis inhibits EMT, stem cell properties and metastasis in colorectal cancer
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Yuling Li1,2,*, Zhenbing Lv1,3,4,*, Guoyang He1,2, Jianmei Wang1,2, Xiaojing Zhang1,5, Guifeng Lu1,2, Xiaoli Ren1,2, Feifei Wang1,2, Xiaohui Zhu1,2, Yi Ding6, Wenting Liao1,2, Yanqing Ding1,2 and Li Liang1,2
1 Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, People’s Republic of China
2 Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, Guangdong Province, People’s Republic of China
3 Department of General Surgery Two, Nanchong Central Hospital, Nanchong city, Sichuan Province, People’s Republic of China
4 The Second Clinical School of Northern Sichuan Medical College, Nanchong city, Sichuan Province, People’s Republic of China
5 Department of Pathology, Shenzhen University, Shenzhen, People’s Republic of China
6 Department of Radiotherapy, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, People’s Republic of China
* These authors contributed equally to this work
Li Liang, email:
Keywords: miR-371-5p, SOX17, SOX2, metastasis, colorectal cancer
Received: January 15, 2015 Accepted: February 10, 2015 Published: March 15, 2015
Cancer stem cells (CSCs) and EMT-type cells, which share molecular characteristics with CSCs, have been believed to play critical roles in tumor metastasis. Although much progress has been garnered in elucidating the molecular pathways that trigger EMT, stemness and metastasis, a number of key mechanistic gaps remain elusive. In the study, miR-371-5p was obviously down-regulated in primary CRC tissues compared with matched adjacent normal mucosa and correlated significantly with differentiation, tumor size, lymphatic and liver metastases. MiR-371-5p could attenuate proliferation, invasion in vitro and metastasis in vivo in CRC cells. It also suppressed EMT by regulating Wnt/β-catenin signaling and strongly decreased the CRC stemness phenotypes. Moreover, demethylation of SOX17 induced miR-371-5p expression and consequently suppressed its direct target SOX2 in CRC cells. MiR-371-5p was necessary for SOX17 mediated cancer-related traits and SOX2 was a functional target of miR-371-5p. A positive relationship between SOX17 and miR-371-5p expression and a negative one between miR-371-5p and SOX2 expression were observed in CRC cell lines and tissues. In conclusion, we identified miR-371-5p as an important “oncosuppressor” in CRC progression and elucidated a novel mechanism of the SOX17/miR-371-5p/SOX2 axis in the regulation of EMT, stemness and metastasis, which may be a potential therapeutic target.
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