title: MicroRNA-125b attenuates epithelial-mesenchymal transitions and targets stem-like liver cancer cells through small mothers against decapentaplegic 2 and 4.
abstract: Emerging evidence suggests that epithelial-mesenchymal transitions (EMTs) play important roles in tumor metastasis and recurrence. Understanding molecular mechanisms that regulate the EMT process is crucial for improving treatment of hepatocellular carcinoma (HCC). MicroRNAs (miRNAs) play important roles in HCC; however, the mechanisms by which miRNAs target the EMT and their therapeutic potential remains largely unknown. To better explore the roles of miRNAs in the EMT process, we established an EMT model in HCC cells by transforming growth factor beta 1 treatment and found that several tumor-related miRNAs were significantly decreased. Among these miRNAs, miR-125b expression was most strongly suppressed. We also found down-regulation of miR-125b in most HCC cells and clinical specimens, which correlated with cellular differentiation in HCC patients. We then demonstrated that miR-125b overexpression attenuated EMT phenotype in HCC cancer cells, whereas knockdown of miR-125b promoted the EMT phenotype in vitro and in vivo. Moreover, we found that miR-125b attenuated EMT-associated traits, including chemoresistance, migration, and stemness in HCC cells, and negatively correlated with EMT and cancer stem cell (CSC) marker expressions in HCC specimens. miR-125b overexpression could inhibit CSC generation and decrease tumor incidence in the mouse xenograft model. Mechanistically, our data revealed that miR-125b suppressed EMT and EMT-associated traits of HCC cells by targeting small mothers against decapentaplegic (SMAD)2 and 4. Most important, the therapeutic delivery of synthetic miR-125b mimics decreased the target molecule of CSC and inhibited metastasis in the mice model. These findings suggest a potential therapeutic treatment of miR-125b for liver cancer.
  
  
  CONCLUSIONS
  miR-125b exerts inhibitory effects on EMT and EMT-associated traits in HCC by SMAD2 and 4. Ectopic expression of miR-125b provides a promising strategy to treat HCC.
authors.affiliation: Stem Cell and Regenerative Medicine Lab, Beijing Institute of Transfusion Medicine, Beijing, China.|South China Research Center for Stem Cell & Regenerative Medicine, AMMS, Guangzhou, China.
authors.forename: Jun-Nian
authors.initials: JN
authors.lastname: Zhou
authors.affiliation: Stem Cell and Regenerative Medicine Lab, Beijing Institute of Transfusion Medicine, Beijing, China.|South China Research Center for Stem Cell & Regenerative Medicine, AMMS, Guangzhou, China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Zeng
authors.affiliation: Stem Cell and Regenerative Medicine Lab, Beijing Institute of Transfusion Medicine, Beijing, China.|South China Research Center for Stem Cell & Regenerative Medicine, AMMS, Guangzhou, China.
authors.forename: Hai-Yang
authors.initials: HY
authors.lastname: Wang
authors.affiliation: Stem Cell and Regenerative Medicine Lab, Beijing Institute of Transfusion Medicine, Beijing, China.|South China Research Center for Stem Cell & Regenerative Medicine, AMMS, Guangzhou, China.
authors.forename: Biao
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Stem Cell and Regenerative Medicine Lab, Beijing Institute of Transfusion Medicine, Beijing, China.|South China Research Center for Stem Cell & Regenerative Medicine, AMMS, Guangzhou, China.
authors.forename: Si-Ting
authors.initials: ST
authors.lastname: Li
authors.affiliation: Stem Cell and Regenerative Medicine Lab, Beijing Institute of Transfusion Medicine, Beijing, China.|South China Research Center for Stem Cell & Regenerative Medicine, AMMS, Guangzhou, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Nan
authors.affiliation: Stem Cell and Regenerative Medicine Lab, Beijing Institute of Transfusion Medicine, Beijing, China.|South China Research Center for Stem Cell & Regenerative Medicine, AMMS, Guangzhou, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Cao
authors.affiliation: Fangshan Traditional Chinese Medicine Hospital, Beijing, China.
authors.forename: Chun-Jiang
authors.initials: CJ
authors.lastname: Fu
authors.affiliation: Stem Cell and Regenerative Medicine Lab, Beijing Institute of Transfusion Medicine, Beijing, China.
authors.forename: Xin-Long
authors.initials: XL
authors.lastname: Yan
authors.affiliation: Stem Cell and Regenerative Medicine Lab, Beijing Institute of Transfusion Medicine, Beijing, China.|South China Research Center for Stem Cell & Regenerative Medicine, AMMS, Guangzhou, China.
authors.forename: Ya-Li
authors.initials: YL
authors.lastname: Jia
authors.affiliation: Stem Cell and Regenerative Medicine Lab, Beijing Institute of Transfusion Medicine, Beijing, China.|South China Research Center for Stem Cell & Regenerative Medicine, AMMS, Guangzhou, China.
authors.forename: Jing-Xue
authors.initials: JX
authors.lastname: Wang
authors.affiliation: Stem Cell and Regenerative Medicine Lab, Beijing Institute of Transfusion Medicine, Beijing, China.
authors.forename: Ai-Hua
authors.initials: AH
authors.lastname: Zhao
authors.affiliation: Department of Hepatobiliary Surgery, Beijing 302 Hospital, Beijing, China.
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Li
authors.affiliation: Stem Cell and Regenerative Medicine Lab, Beijing Institute of Transfusion Medicine, Beijing, China.|South China Research Center for Stem Cell & Regenerative Medicine, AMMS, Guangzhou, China.
authors.forename: Yan-Hua
authors.initials: YH
authors.lastname: Li
authors.affiliation: Stem Cell and Regenerative Medicine Lab, Beijing Institute of Transfusion Medicine, Beijing, China.|South China Research Center for Stem Cell & Regenerative Medicine, AMMS, Guangzhou, China.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Xie
authors.affiliation: Department of Gastroenterology & Hepatology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Xiao-Mei
authors.initials: XM
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology & Hepatology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Department of Hepatobiliary Surgery, Beijing Tongren Hospital, Beijing, China.
authors.forename: Ying-Chen
authors.initials: YC
authors.lastname: Xu
authors.affiliation: Stem Cell and Regenerative Medicine Lab, Beijing Institute of Transfusion Medicine, Beijing, China.|South China Research Center for Stem Cell & Regenerative Medicine, AMMS, Guangzhou, China.
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: He
authors.affiliation: Stem Cell and Regenerative Medicine Lab, Beijing Institute of Transfusion Medicine, Beijing, China.|South China Research Center for Stem Cell & Regenerative Medicine, AMMS, Guangzhou, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Yue
authors.affiliation: Stem Cell and Regenerative Medicine Lab, Beijing Institute of Transfusion Medicine, Beijing, China.|South China Research Center for Stem Cell & Regenerative Medicine, AMMS, Guangzhou, China.
authors.forename: Xue-Tao
authors.initials: XT
authors.lastname: Pei
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D011897:Random Allocation; D012680:Sensitivity and Specificity; D051899:Smad2 Protein / Q000378:metabolism*; D051901:Smad4 Protein / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D035683:MicroRNAs; C527468:Mirn125 microRNA, mouse; D051899:Smad2 Protein; C497783:Smad2 protein, mouse; D051901:Smad4 Protein