Inhibiting inducible miR-223 further reduces viable cells in human cancer cell lines MCF-7 and PC3 treated by celastrol
Authors: Yufan Shen
Xue Zhang
Bin Peng
Denghai Zhang
Fanfan Cao
Lu Cao
Chunxin Yang
Georges Uzan
Ying Wang
Journal: BMC Cancer (2015)
Discipline: CLINICAL MEDICINE
Keywords: Celastrol; miR-223; NF-κB; mTOR; breast cancer
Affiliations: Department of Clinical Laboratory Diagnostics, Postgraduate Education College, Ningxia Medical University, Yinchuan, 750004, China. ., Sino-French Cooperative Central Lab, Shanghai Gongli Hospital, the Second Military Medical University, 207 Ju Ye Road, Pudong New District, Shanghai, 200135, China. ., Pharmaceutical Department, Zhong Shan Hospital, Shanghai Fudan University, 136 Yi Xue Yuan Road, Shanghai, 200032, China. ., U972, Inserm, Bâtiment Lavoisier, Hôpital Paul Brousse, 12 Avenue Paul Vaillant Couturier, 94807, Villejuif Cedex, France. .

Abstract:  Background: Celastrol is a novel anti-tumor agent. Ways to further enhance this effect of celastrol has attracted much research attention. Methods and 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. 

Retracted: No

PubPeer comments:
 (a) The authors defined the notion of u201c**cloud**u201d in Definition 1 and some operations in Definition 2. However, it seems that the operation $Atimes B$ may lead to unreasonable results. For example, let $$A=(0, 1, 1)qquad B=(0, 1, 1)$$ According to Definition 1, it follows that $$Atimes B =(0,0,0)$$ The result is a fixed value zero according to the illustration in Figure 1. However, this is not reasonable according to the context. (b) After Definition 3, the authors presented the u201c**forward generator**u201d for a cloud with given parameters. In Definition 5, the authors further proposed a method to construct some clouds on a given universe $[X_{min}, X_{max}]$. An illustration for such a procedure is presented in Example 3. However, such a procedure is not consistent with the u201c**forward generator**u201d for a cloud. For instance, **the universe set given in Example 3 is $[0, 10]$** and two of the clouds are constructed as $$Y_{-2}=(0, 1.031, 0.262)qquad Y_2=(10, 1.031, 0.262)$$ According to the u201c**forward generator**u201d, the points generated from $Y_{-2}$ and $Y_2$ may contain values beyond the universe set $[0, 10]$. This is not consistent with the conventional use of the notion u201cuniverseu201d. Can the authors kindly address these issues? ![file] ![file] ![file] ![file] ![file] ![file] ,