title: miR-101 targeting ZFX suppresses tumor proliferation and metastasis by regulating the MAPK/Erk and Smad pathways in gallbladder carcinoma.
abstract: Gallbladder cancer (GBC), the most common malignancy of the bile duct, is highly aggressive and has an extremely poor prognosis, which is a result of early metastasis. As it is regulated being at multiple levels, the metastatic cascade in GBC is complex. Recent evidence suggests that microRNAs (miRNAs) are involved in cancer metastasis and are promising therapeutic targets. In this study, miR-101 was significantly downregulated in tumor tissues, particularly in metastatic tissues. In GBC patients, low miR-101 expression was correlated with tumor size, tumor invasion, lymph node metastasis, TNM stage, and poor survival. Moreover, miR-101 was an independent prognostic marker for GBC. Additionally, miR-101 inhibited GBC cell proliferation, migration, invasion, and TGF-β-induced epithelial-mesenchymal transition (EMT) in vitro and in vivo. Mechanistically, the gene encoding the zinc finger protein X-linked (ZFX) was identified as a direct target of miR-101. More importantly, miR-101 significantly reduced activation of the MAPK/Erk and Smad signaling pathways, resulting in inhibition of TGF-β-mediated induction of EMT. Altogether, our findings demonstrate a novel mechanism by which miR-101 attenuates the EMT and metastasis in GBC cells and suggest that miR-101 can serve as a potential biomarker and therapeutic target for GBC management.
authors.affiliation: Department and Laboratory of General Surgery, Xinhua Hospital, Affiliated with Shanghai Jiao Tong University, School of Medicine, Shanghai 200092, China.|Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors.forename: Run-Fa
authors.initials: RF
authors.lastname: Bao
authors.affiliation: Department and Laboratory of General Surgery, Xinhua Hospital, Affiliated with Shanghai Jiao Tong University, School of Medicine, Shanghai 200092, China.|Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors.forename: Yi-Jun
authors.initials: YJ
authors.lastname: Shu
authors.affiliation: Department and Laboratory of General Surgery, Xinhua Hospital, Affiliated with Shanghai Jiao Tong University, School of Medicine, Shanghai 200092, China.|Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors.forename: Yun-Ping
authors.initials: YP
authors.lastname: Hu
authors.affiliation: Department and Laboratory of General Surgery, Xinhua Hospital, Affiliated with Shanghai Jiao Tong University, School of Medicine, Shanghai 200092, China.|Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors.forename: Xu-An
authors.initials: XA
authors.lastname: Wang
authors.affiliation: Department and Laboratory of General Surgery, Xinhua Hospital, Affiliated with Shanghai Jiao Tong University, School of Medicine, Shanghai 200092, China.|Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department and Laboratory of General Surgery, Xinhua Hospital, Affiliated with Shanghai Jiao Tong University, School of Medicine, Shanghai 200092, China.|Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors.forename: Hai-Bin
authors.initials: HB
authors.lastname: Liang
authors.affiliation: Department and Laboratory of General Surgery, Xinhua Hospital, Affiliated with Shanghai Jiao Tong University, School of Medicine, Shanghai 200092, China.|Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Ye
authors.affiliation: Department and Laboratory of General Surgery, Xinhua Hospital, Affiliated with Shanghai Jiao Tong University, School of Medicine, Shanghai 200092, China.|Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors.forename: Huai-Feng
authors.initials: HF
authors.lastname: Li
authors.affiliation: Department and Laboratory of General Surgery, Xinhua Hospital, Affiliated with Shanghai Jiao Tong University, School of Medicine, Shanghai 200092, China.|Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors.forename: Shan-Shan
authors.initials: SS
authors.lastname: Xiang
authors.affiliation: Department and Laboratory of General Surgery, Xinhua Hospital, Affiliated with Shanghai Jiao Tong University, School of Medicine, Shanghai 200092, China.|Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Weng
authors.affiliation: Department and Laboratory of General Surgery, Xinhua Hospital, Affiliated with Shanghai Jiao Tong University, School of Medicine, Shanghai 200092, China.|Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department and Laboratory of General Surgery, Xinhua Hospital, Affiliated with Shanghai Jiao Tong University, School of Medicine, Shanghai 200092, China.|Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors.forename: Xiang-Song
authors.initials: XS
authors.lastname: Wu
authors.affiliation: Department and Laboratory of General Surgery, Xinhua Hospital, Affiliated with Shanghai Jiao Tong University, School of Medicine, Shanghai 200092, China.|Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors.forename: Mao-Lan
authors.initials: ML
authors.lastname: Li
authors.affiliation: Department and Laboratory of General Surgery, Xinhua Hospital, Affiliated with Shanghai Jiao Tong University, School of Medicine, Shanghai 200092, China.|Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors.forename: Wen-Guang
authors.initials: WG
authors.lastname: Wu
authors.affiliation: Department and Laboratory of General Surgery, Xinhua Hospital, Affiliated with Shanghai Jiao Tong University, School of Medicine, Shanghai 200092, China.|Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors.forename: Yi-Jian
authors.initials: YJ
authors.lastname: Zhang
authors.affiliation: Department and Laboratory of General Surgery, Xinhua Hospital, Affiliated with Shanghai Jiao Tong University, School of Medicine, Shanghai 200092, China.|Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department and Laboratory of General Surgery, Xinhua Hospital, Affiliated with Shanghai Jiao Tong University, School of Medicine, Shanghai 200092, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Dong
authors.affiliation: Department and Laboratory of General Surgery, Xinhua Hospital, Affiliated with Shanghai Jiao Tong University, School of Medicine, Shanghai 200092, China.|Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors.forename: Ying-Bin
authors.initials: YB
authors.lastname: Liu
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D049109:Cell Proliferation / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D005706:Gallbladder Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D064593:Heterografts; D006801:Humans; D053208:Kaplan-Meier Estimate; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D011379:Prognosis; D016016:Proportional Hazards Models; D051785:Smad Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D051741:Kruppel-Like Transcription Factors; C534072:MIRN101 microRNA, human; D035683:MicroRNAs; D051785:Smad Proteins; C062076:zinc finger protein, X-linked
keywords: EMT; TGF-β; ZFX; gallbladder carcinoma; miR-101