RNA interference targeting slug increases cholangiocarcinoma cell sensitivity to cisplatin via upregulating PUMA
Authors: Jigang Wang
Kejun Zhang
Yuan Gao
Xingang Wang
Shaoyan Zhang
Bomin Yan
Dong Chen
Journal: International Journal of Molecular Sciences (2011)
Discipline: CHEMISTRY
Keywords: E-cadherin; PUMA; chemotherapy; cisplatin; slug.
Affiliations: General Surgery of the Affiliated Hospital of Medical College, Qingdao University, Qingdao, Shan Dong Province 266003, China; E-Mails: wl (K.Z);  (X.W.);  (B.Y.).

Abstract:  Slug is an E-cadherin repressor and a suppressor of PUMA (p53 upregulated modulator of apoptosis) and it has recently been demonstrated that Slug plays an important role in controlling apoptosis. In this study, we examined whether Slug's ability to silence expression suppresses the growth of cholangiocarcinoma cells and/or sensitizes cholangiocarcinoma cells to chemotherapeutic agents through induction of apoptosis. We targeted the Slug gene using siRNA (Slug siRNA) via full Slug cDNA plasmid (Slug cDNA) transfection of cholangiocarcinoma cells. Slug siRNA, cisplatin, or Slug siRNA in combination with cisplatin, were used to treat cholangiocarcinoma cells in vitro. Western blot was used to detect the expression of Slug, PUMA, and E-cadherin protein. TUNEL, Annexin V Staining, and cell cycle analysis were used to detect apoptosis. A nude mice subcutaneous xenograft model of QBC939 cells was used to assess the effect of Slug silencing and/or cisplatin on tumor growth. Immunohistochemical staining was used to analyze the expression of Slug and PUMA. TUNEL was used to detect apoptosis in vivo. The results showed that PUMA and E-cadherin expression in cholangiocarcinoma cells is Slug dependent. We demonstrated that Slug silencing and cisplatin both promote apoptosis by upregulation of PUMA, not by upregulation of E-cadherin. Slug silencing significantly sensitized cholangiocarcinoma cells to cisplatin through upregulation of PUMA. Finally, we showed that Slug silencing suppressed the growth of QBC939 xenograft tumors and sensitized the tumor cells to cisplatin through PUMA upregulation and induction of apoptosis. Our findings indicate that Slug is an important modulator of the therapeutic response of cholangiocarcinoma cells and is potentially useful as a sensitizer in cholangiocarcinoma therapy. One of the mechanisms is the regulation of PUMA by Slug. 

Retracted: Yes

PubPeer comments:
 2017 retraction. http: www.mdpi.com 1422-0067 18 7 1483 htm , 
 The two articles [1,2] published in the International Journal of Molecular Sciences will be retracted. An investigation of the peer review process has concluded that it was compromised via the use of fake reviewer email addresses provided by the authors. MDPI takes the integrity of its review process very seriously. Since bringing the management of the peer review process in-house in 2006 [3], we have had in place criteria for inviting peer reviewers which include confirmation of their identity, especially for reviewers suggested by authors. In the years since the publication of [1] and [2], we have further updated the technology available to editors in order to mitigate against the possibility that review reports could be faked by the authors. An internal investigation has concluded that for these two papers the procedures were not correctly followed, for which we apologize to the readers of the journal. The investigation covered all MDPI journals and these were the only problematic cases discovered. We believe that the vast majority of authors submit manuscripts in good will, however we remain vigilant for suspicious activity and strive to have robust procedures in place to ensure that such cases can be discovered prior to publication. ,