title: Snail and Slug collaborate on EMT and tumor metastasis through miR-101-mediated EZH2 axis in oral tongue squamous cell carcinoma.
abstract: microRNAs(miRNAs) can regulate epithelial-mesenchymal transition (EMT) through transcription factors, however, little is known whether EMT transcription factors can modulate miRNAs and further induce EMT and cancer metastasis. Here we show that overexpression of Snail and Slug leads to a mesenchymal phenotype and morphology and enhances cell invasion along with stem cell properties in squamous cell carcinoma of oral tongue (OTSCC) cells. Repression of miR-101 expression by Snail and Slug is essential for Snail/Slug-induced malignant phenotypes. The suppression of miR-101 subsequently activates EZH2, the sole histone methyltransferase, inducing EMT, migration and invasion of OTSCC cells. Importantly, co-overexpression of Slug and Snail correlates with poor survival and elevated EZH2 expression in two independent patient cohorts of OTSCC specimens. These findings defined a Snail and Slug/miR-101/EZH2 pathway as a novel regulatory axis of EMT-mediated-microRNA signaling.
authors.affiliation: State Key Laboratory of Oral Diseases West China Hospital of Stomatology (Sichuan University), Chengdu Sichuan 610041, People's Republic of China.|Department of Stomatology, Zhoushan Hospital, Zhoushan, Zhejiang 316000, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Oral Diseases West China Hospital of Stomatology (Sichuan University), Chengdu Sichuan 610041, People's Republic of China.
authors.forename: Ya-ping
authors.initials: YP
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Oral Diseases West China Hospital of Stomatology (Sichuan University), Chengdu Sichuan 610041, People's Republic of China.|Department of Oral and Maxillofacial Surgery, Tianjin Stomatological Hospital, Tianjin 300041, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Oral Diseases West China Hospital of Stomatology (Sichuan University), Chengdu Sichuan 610041, People's Republic of China.
authors.forename: Kai-de
authors.initials: KD
authors.lastname: Li
authors.affiliation: State Key Laboratory of Oral Diseases West China Hospital of Stomatology (Sichuan University), Chengdu Sichuan 610041, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Oral Diseases West China Hospital of Stomatology (Sichuan University), Chengdu Sichuan 610041, People's Republic of China.
authors.forename: Shi-yu
authors.initials: SY
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Oral Diseases West China Hospital of Stomatology (Sichuan University), Chengdu Sichuan 610041, People's Republic of China.
authors.forename: Hao
authors.initials: H
authors.lastname: Feng
authors.affiliation: State Key Laboratory of Oral Diseases West China Hospital of Stomatology (Sichuan University), Chengdu Sichuan 610041, People's Republic of China.
authors.forename: Sha-sha
authors.initials: SS
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Oral Diseases West China Hospital of Stomatology (Sichuan University), Chengdu Sichuan 610041, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Oral Diseases West China Hospital of Stomatology (Sichuan University), Chengdu Sichuan 610041, People's Republic of China.
authors.forename: Xiang-rui
authors.initials: XR
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Oral Diseases West China Hospital of Stomatology (Sichuan University), Chengdu Sichuan 610041, People's Republic of China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Cen
authors.affiliation: Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei University of Technology, Wuhan 430068, People's Republic of China.
authors.forename: Ya-jie
authors.initials: YJ
authors.lastname: Tang
authors.affiliation: State Key Laboratory of Oral Diseases West China Hospital of Stomatology (Sichuan University), Chengdu Sichuan 610041, People's Republic of China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Oral Diseases West China Hospital of Stomatology (Sichuan University), Chengdu Sichuan 610041, People's Republic of China.
authors.forename: Yun-feng
authors.initials: YF
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Oral Diseases West China Hospital of Stomatology (Sichuan University), Chengdu Sichuan 610041, People's Republic of China.|Department of Oral Pathology, West China Hospital of Stomatology (Sichuan University), Chengdu Sichuan 610041, People's Republic of China.
authors.forename: Ya-ling
authors.initials: YL
authors.lastname: Tang
authors.affiliation: State Key Laboratory of Oral Diseases West China Hospital of Stomatology (Sichuan University), Chengdu Sichuan 610041, People's Republic of China.|Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology (Sichuan University), Chengdu Sichuan 610041, People's Republic of China.
authors.forename: Xin-hua
authors.initials: XH
authors.lastname: Liang
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000556:secondary; D045744:Cell Line, Tumor; D002465:Cell Movement; D000071221:Enhancer of Zeste Homolog 2 Protein; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D063151:Polycomb Repressive Complex 2 / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D016016:Proportional Hazards Models; D034622:RNA Interference; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors; D000077195:Squamous Cell Carcinoma of Head and Neck; D013997:Time Factors; D014062:Tongue Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: C534072:MIRN101 microRNA, human; D035683:MicroRNAs; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2
keywords: Slug; Snail; epithelial-mesenchymal transition (EMT); miR-101; oral tongue squamous cell carcinoma (OTSCC)