title: Inhibiting inducible miR-223 further reduces viable cells in human cancer cell lines MCF-7 and PC3 treated by celastrol.
abstract: BACKGROUND
  Celastrol is a novel anti-tumor agent. Ways to further enhance this effect of celastrol has attracted much research attention.
  
  
  RESULTS
  Here, we report that celastrol treatment can elevate miR-223 in human breast cancer cell line MCF-7 and prostate cancer PC3. Down-regulating miR-223 could increase the number of viable cells, yet it further reduced viable cells in samples that were treated by celastrol; up-regulation of miR-223 displayed opposite effects. Celastrol's miR-223 induction might be due to NF-κB inhibition and transient mTOR activation: these two events occurred prior to miR-223 elevation in celastrol-treated cells. NF-κB inhibitor, like celastrol, could induce miR-223; the induction of miR-223 by NF-κB inhibitor or celastrol was reduced by the use of mTOR inhibitor. Finally and interestingly, miR-223 also could affect NF-κB and mTOR and the effects were different between cells treated or not treated with celastrol, thus providing an explanation for differing effects of miR-223 alteration on cellular viability in the presence of celastrol or not.
  
  
  CONCLUSIONS
  For the first time, we disclose that celastrol could induce miR-223 in breast and prostate cancer cells, and that inhibiting miR-223 could further reduce the living cells in celastrol-treated cancer cell lines. We thus provide a novel way to increase celastrol's anti-cancer effects.
authors.affiliation: Department of Clinical Laboratory Diagnostics, Postgraduate Education College, Ningxia Medical University, Yinchuan, 750004, China. c645353030@163.com.|Sino-French Cooperative Central Lab, Shanghai Gongli Hospital, the Second Military Medical University, 207 Ju Ye Road, Pudong New District, Shanghai, 200135, China. c645353030@163.com.
authors.forename: Lu
authors.initials: L
authors.lastname: Cao
authors.affiliation: Department of Clinical Laboratory Diagnostics, Postgraduate Education College, Ningxia Medical University, Yinchuan, 750004, China. 13524805404@139.com.|Sino-French Cooperative Central Lab, Shanghai Gongli Hospital, the Second Military Medical University, 207 Ju Ye Road, Pudong New District, Shanghai, 200135, China. 13524805404@139.com.
authors.forename: Xue
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Sino-French Cooperative Central Lab, Shanghai Gongli Hospital, the Second Military Medical University, 207 Ju Ye Road, Pudong New District, Shanghai, 200135, China. yffs1121@hotmail.com.
authors.forename: Fanfan
authors.initials: F
authors.lastname: Cao
authors.affiliation: Sino-French Cooperative Central Lab, Shanghai Gongli Hospital, the Second Military Medical University, 207 Ju Ye Road, Pudong New District, Shanghai, 200135, China. ying402407@163.com.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Clinical Laboratory Diagnostics, Postgraduate Education College, Ningxia Medical University, Yinchuan, 750004, China. 458244528@qq.com.|Sino-French Cooperative Central Lab, Shanghai Gongli Hospital, the Second Military Medical University, 207 Ju Ye Road, Pudong New District, Shanghai, 200135, China. 458244528@qq.com.
authors.forename: Yufan
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Pharmaceutical Department, Zhong Shan Hospital, Shanghai Fudan University, 136 Yi Xue Yuan Road, Shanghai, 200032, China. ycx508@126.com.
authors.forename: Chunxin
authors.initials: C
authors.lastname: Yang
authors.affiliation: Sino-French Cooperative Central Lab, Shanghai Gongli Hospital, the Second Military Medical University, 207 Ju Ye Road, Pudong New District, Shanghai, 200135, China. georges.uzan@inserm.fr.|U972, Inserm, Bâtiment Lavoisier, Hôpital Paul Brousse, 12 Avenue Paul Vaillant Couturier, 94807, Villejuif Cedex, France. georges.uzan@inserm.fr.
authors.forename: Georges
authors.initials: G
authors.lastname: Uzan
authors.affiliation: Sino-French Cooperative Central Lab, Shanghai Gongli Hospital, the Second Military Medical University, 207 Ju Ye Road, Pudong New District, Shanghai, 200135, China. lily_1001pb@163.com.|U972, Inserm, Bâtiment Lavoisier, Hôpital Paul Brousse, 12 Avenue Paul Vaillant Couturier, 94807, Villejuif Cedex, France. lily_1001pb@163.com.
authors.forename: Bin
authors.initials: B
authors.lastname: Peng
authors.affiliation: Sino-French Cooperative Central Lab, Shanghai Gongli Hospital, the Second Military Medical University, 207 Ju Ye Road, Pudong New District, Shanghai, 200135, China. shanghai_zhang@hotmail.com.|U972, Inserm, Bâtiment Lavoisier, Hôpital Paul Brousse, 12 Avenue Paul Vaillant Couturier, 94807, Villejuif Cedex, France. shanghai_zhang@hotmail.com.
authors.forename: Denghai
authors.initials: D
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D008297:Male; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D053978:Pentacyclic Triterpenes; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D014315:Triterpenes / Q000008:administration & dosage*
chemical_list: D035683:MicroRNAs; D016328:NF-kappa B; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; C525067:MIR223, human; C050414:celastrol