title: The SOX17/miR-371-5p/SOX2 axis inhibits EMT, stem cell properties and metastasis in colorectal cancer.
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.
authors: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, People's Republic of China.|Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, Guangdong Province, People's Republic of China.
authors: Yuling
authors: Y
authors: Li
authors: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, People's Republic of China.|Department of General Surgery Two, Nanchong Central Hospital, Nanchong city, Sichuan Province, People's Republic of China.|The Second Clinical School of Northern Sichuan Medical College, Nanchong City, Sichuan Province, People's Republic of China.
authors: Zhenbing
authors: Z
authors: Lv
authors: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, People's Republic of China.|Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, Guangdong Province, People's Republic of China.
authors: Guoyang
authors: G
authors: He
authors: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, People's Republic of China.|Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, Guangdong Province, People's Republic of China.
authors: Jianmei
authors: J
authors: Wang
authors: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, People's Republic of China.|Department of Pathology, Shenzhen University, Shenzhen, People's Republic of China.
authors: Xiaojing
authors: X
authors: Zhang
authors: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, People's Republic of China.|Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, Guangdong Province, People's Republic of China.
authors: Guifeng
authors: G
authors: Lu
authors: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, People's Republic of China.|Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, Guangdong Province, People's Republic of China.
authors: Xiaoli
authors: X
authors: Ren
authors: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, People's Republic of China.|Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, Guangdong Province, People's Republic of China.
authors: Feifei
authors: F
authors: Wang
authors: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, People's Republic of China.|Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, Guangdong Province, People's Republic of China.
authors: Xiaohui
authors: X
authors: Zhu
authors: Department of Radiotherapy, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, People's Republic of China.
authors: Yi
authors: Y
authors: Ding
authors: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, People's Republic of China.|Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, Guangdong Province, People's Republic of China.
authors: Wenting
authors: W
authors: Liao
authors: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, People's Republic of China.|Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, Guangdong Province, People's Republic of China.
authors: Yanqing
authors: Y
authors: Ding
authors: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, People's Republic of China.|Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, Guangdong Province, People's Republic of China.
authors: Li
authors: L
authors: Liang
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology / Q000503:physiopathology* / Q000556:secondary; D000818:Animals; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000473:pathology / Q000503:physiopathology*; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D008113:Liver Neoplasms / Q000556:secondary; D008175:Lung Neoplasms / Q000556:secondary; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000502:physiology; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000503:physiopathology*; D009363:Neoplasm Proteins / Q000502:physiology*; D014411:Neoplastic Stem Cells / Q000166:cytology*; D039904:Pluripotent Stem Cells / Q000166:cytology; D012334:RNA, Neoplasm; D055748:SOXB1 Transcription Factors / Q000502:physiology; D055760:SOXF Transcription Factors / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013047:Specific Pathogen-Free Organisms; D014161:Transduction, Genetic; D060449:Wnt Signaling Pathway
chemical_list: C554834:MIRN371 microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; C109188:SOX17 protein, human; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D055760:SOXF Transcription Factors
keywords: SOX17; SOX2; colorectal cancer; metastasis; miR-371-5p