IL-26 promotes the proliferation and survival of human gastric cancer cells by regulating the balance of STAT1 and STAT3 activation
Authors: Wei You
Chunrong Gu
Jindao Wu
Zhengshan Wu
Xiangcheng Li
Qiyun Tang
Chuanyong Zhang
Journal: PloS one (2013)
Discipline: Multidisciplinary
Keywords: Interleukin-26; Th17 cells; human gastric cancer; IL-20R1; STAT1
Affiliations: Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, PR China.

Abstract:  Interleukin-26 (IL-26) is one of the cytokines secreted by Th17 cells whose role in human tumors remains unknown. Here, we investigated the expression and potential role of IL-26 in human gastric cancer (GC). The expression of IL-26 and related molecules such as IL-20R1, STAT1 and STAT3 was examined by real-time PCR and immunohistochemisty. The effects of IL-26 on cell proliferation and cisplatin-induced apoptosis were analyzed by BrdU cooperation assay and PI-Annexin V co-staining, respectively. Lentiviral mediated siRNA was used to explore its mechanism of action, and IL-26 related signaling was analyzed by western blotting. Human GC tissues showed increased levels of IL-26 and its related molecules and activation of STAT3 signaling, whereas STAT1 activation did not differ significantly between GC and normal gastric tissues. Moreover, IL-26 was primarily produced by Th17 and NK cells. IL-26 promoted the proliferation and survival of MKN45 and SGC-7901 gastric cancer cells in a dose-dependent manner. Furthermore, IL-20R2 and IL-10R1, which are two essential receptors for IL-26 signaling, were expressed in both cell lines. IL-26 activated STAT1 and STAT3 signaling; however, the upregulation of the expression of Bcl-2, Bcl-xl and c-myc indicated that the effect of IL-26 is mediated by STAT3 activation. Knockdown of STAT1 and STAT3 expression suggested that the proliferative and anti-apoptotic effects of IL-26 are mediated by the modulation of STAT1/STAT3 activation. In summary, elevated levels of IL-26 in human GC promote proliferation and survival by modulating STAT1/STAT3 signaling. 

Retracted: No

PubPeer comments:
null, 
 Reposting the concerns about Figures 3 and 5: ![file] , 
 Retracted, 15 September 2022: https: journals.plos.org plosone article?id=10.1371 journal.pone.0274980  Following the publication of this article [1], concerns were raised regarding the results presented in Figs 1, 2, 3, 4, and 5. Specifically, * In Fig 1C, the IL-20R1 N.C. panel appears to partially overlap with the STAT3 (S727) N.C. panel. * The FACS data presented in the panels listed below appear more similar than would be expected from independent samples: u25cb Fig 2A: a1, a2, a3, a4, a5, a6, a7, b1, b2. u25cb Fig 3B: MKN45, MKN45+1ng ml IL-26, MKN45+10ng ml, MKN45+50ng ml IL-26, SGC7901, SGC7901+1ng ml IL-26, SGC7901+10ng ml IL-26, and SGC7901+50ng ml IL-26. u25cb Fig 5C: MKNcs+10ng ml IL-26, MKN-STAT1siRNA+10ng nl IL-26, SGC7901cs+10ng ml IL-26, SGC7901-STAT1siRNA+10ng ml IL-26, and SGC7901-STAT3siRNA+10ng ml IL-26. * Irregularities have been detected in the background of the following panels u25cb Fig 4A IL-20R1 panel u25cb Fig 4B Bcl-xl panel u25cb Fig 5A STAT1 panel The authors did not respond to the editorial queries about these concerns, nor did they provide the original data underlying the results presented in this article. In the absence of the original data underlying the published results, these issues cannot be resolved. In light of the concerns affecting multiple figure panels that question the integrity of these data, the PLOS ONE Editors retract this article. All authors either did not respond directly or could not be reached. ,