IL-26 promotes the proliferation and survival of human gastric cancer cells by regulating the balance of STAT1 and STAT3 activation.
IL-26 promotes the proliferation and survival of human gastric cancer cells by regulating the balance of STAT1 and STAT3 activation.
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IL-26通过调节STAT1和STAT3激活的平衡促进人胃癌细胞的增殖和存活。
DOI：
10.1371/journal.pone.0063588
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Li X
中科院分区：
文献类型：
--
作者：
You W;Tang Q;Zhang C;Wu J;Gu C;Wu Z;Li X
白细胞介素-26（IL-26）是Th 17细胞分泌的细胞因子之一，其在人类肿瘤中的作用尚不清楚。本研究旨在探讨IL-26在人胃癌中的表达及其可能的作用。实时荧光定量PCR和免疫组化法检测IL-26及相关分子IL-20 R1、STAT 1和STAT 3的表达。采用BrdU协同法和PI-Annexin V共染色法检测IL-26对细胞增殖和顺铂诱导的细胞凋亡的影响。利用慢病毒介导的siRNA探讨其作用机制，并通过Western blotting分析IL-26相关信号通路。人胃癌组织中IL-26及其相关分子水平升高，STAT 3信号转导激活，而STAT 1激活在胃癌和正常胃组织中无显著差异。此外，IL-26主要由Th 17和NK细胞产生。IL-26对胃癌细胞株MKN-45和SGC-7901的增殖和存活有促进作用，且呈剂量依赖性。此外，IL-26信号传导的两种必需受体IL-20 R2和IL-10 R1在两种细胞系中表达。IL-26激活STAT 1和STAT 3信号;然而，Bcl-2，Bcl-xl和c-myc表达的上调表明IL-26的作用是通过STAT 3激活介导的。STAT 1和STAT 3表达的敲低表明IL-26的增殖和抗凋亡作用是通过调节STAT 1/STAT 3活化介导的。总之，人GC中IL-26水平升高通过调节STAT 1/STAT 3信号传导促进增殖和存活。
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.
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影响因子：
64.8
作者：
Cella, Marina;Fuchs, Anja;Vermi, William;Facchetti, Fabio;Otero, Karel;Lennerz, Jochen K. M.;Doherty, Jason M.;Mills, Jason C.;Colonna, Marco
通讯作者：
Colonna, Marco
影响因子：
2
作者：
Fitzpatrick LR
通讯作者：
Fitzpatrick LR
幽门螺杆菌胃上皮细胞粘附和 CagA 注射的分子机制。
DOI：
10.1186/1478-811x-9-28
发表时间：
2011-11-01
期刊：
Cell communication and signaling : CCS
影响因子：
--
作者：
Backert S;Clyne M;Tegtmeyer N
通讯作者：
Tegtmeyer N
影响因子：
32.4
作者：
Stark GR;Darnell JE Jr
通讯作者：
Darnell JE Jr
影响因子：
20.3
作者：
Hughes, Tiffany;Becknell, Brian;Caligiuri, Michael A.
通讯作者：
Caligiuri, Michael A.