Abstract
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.
Highlights
Colorectal cancer (CRC) is the third most common cancer worldwide and the fourth most common cause of death in China
Real-time PCR analyses showed that miR-371-5p was obviously downregulated in 6 CRC cell lines compared with normal colon mucosa
We evaluated its expression in CRC cell lines and 100 paired cases of human primary CRC tissues
Summary
Colorectal cancer (CRC) is the third most common cancer worldwide and the fourth most common cause of death in China. The high mortality of CRC could, in part, be due to high propensity for recurrence and metastasis [1]. In addition to remodeling the microenvironment to facilitate metastasis, cancer cells turn on embryonic morphogenesis regulators to undergo the epithelialmesenchymal transition (EMT) and turn off differentiation programs [2], allowing cancer cells to gain motility, invasion and acquire stem-like properties [3]. Www.impactjournals.com/oncotarget cancer stem cells (CSCs) and EMT-type cells, which share molecular characteristics with CSCs, have been believed to play critical roles in tumor metastasis [4]. CSCs and the EMT process can drive metastatic tumor formation in breast cancer [5]. Molecular knowledge of metastasis in relation to CSCs and EMT in CRC remains unclear
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
