Small interfering RNA (siRNA)-mediated knockdown of macrophage migration inhibitory factor (MIF) suppressed cyclin D1 expression and hepatocellular carcinoma cell proliferation.
Small interfering RNA (siRNA)-mediated knockdown of macrophage migration inhibitory factor (MIF) suppressed cyclin D1 expression and hepatocellular carcinoma cell proliferation.
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小干扰 RNA (siRNA) 介导的巨噬细胞迁移抑制因子 (MIF) 敲低可抑制细胞周期蛋白 D1 表达和肝细胞癌细胞增殖
DOI：
10.18632/oncotarget.2141
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发表时间：
2014-07-30
期刊：
影响因子：
--
通讯作者：
Xia JT
中科院分区：
文献类型：
--
作者：
Huang XH;Jian WH;Wu ZF;Zhao J;Wang H;Li W;Xia JT
巨噬细胞移动抑制因子（Macrophage migration inhibitor factor，MIF）是一种具有免疫调节功能的趋化因子，在肿瘤相关的生物学过程中发挥重要作用。然而，很少有研究集中在肝细胞癌细胞（HCC）中MIF和细胞周期蛋白D1表达的临床相关性。在这项研究中，MIF和细胞周期蛋白D1在肝癌组织和细胞系的表达水平显着上调与邻近的正常组织或正常肝细胞系。在HCC标本中，MIF表达与cyclin D1表达呈正相关。此外，MIF和cyclin D1的表达与肿瘤大小呈正相关。MIF基因敲低可抑制肝癌细胞株PLC和HepG 2的增殖，促进凋亡。然而，针对MIF的小干扰RNA（siRNA）并不影响这些细胞的细胞周期。在体内异种移植模型中，MIF敲低降低了肿瘤生长速率。MIF-knockdown细胞Bcl-2、p-caspase-3、BIM和Bax的表达水平上调，cyclin D1、p-Akt和p-ERK的表达水平下调。这些发现表明，MIF siRNA降低了HCC细胞的增殖并增加了细胞凋亡。MIF基因敲低可抑制生长相关蛋白的表达并诱导凋亡相关蛋白的表达，支持MIF作为HCC新的治疗靶点的作用。
Macrophage migration inhibitory factor (MIF), a proinflammatory and immunoregulatory chemokine, plays important roles in cancer-related biological processes. However, few studies have focused on the clinical relevance of MIF and cyclin D1 expression in hepatocellular carcinoma cells (HCCs). In this study, MIF and cyclin D1 expression levels in HCC tissues and cell lines were significantly upregulated compared with adjacent normal tissues or a normal liver cell line. In HCC specimens, MIF expression positively correlated with cyclin D1 expression. Additionally, MIF and cyclin D1 expression positively correlated with tumor size. MIF knockdown inhibited the proliferation of PLC and HepG2 cells and promoted apoptosis. However, small interfering RNA (siRNA) against MIF did not influence the cell cycle in these cells. In an in vivo xenograft model, MIF knockdown reduced the tumor growth rate. The expression levels of Bcl-2, p-caspase-3, BIM and Bax were upregulated, while the expression levels of cyclin D1, p-Akt and p-ERK were downregulated in MIF-knockdown cells. These findings indicate that MIF siRNA reduces proliferation and increases apoptosis in HCC cells. MIF knockdown inhibits the expression of growth-related proteins and induces the expression of apoptosis-related proteins, supporting a role for MIF as a novel therapeutic target for HCC.
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影响因子：
13.5
作者：
Llovet, Josep M.;Bruix, Jordi
通讯作者：
Bruix, Jordi
影响因子：
32.4
作者：
Shi, Xuerong;Leng, Lin;Bucala, Richard
通讯作者：
Bucala, Richard
DOI：
10.6004/jnccn.2013.0086
发表时间：
2013-06-01
期刊：
Journal of the National Comprehensive Cancer Network : JNCCN
影响因子：
--
作者：
Lauring J;Park BH;Wolff AC
通讯作者：
Wolff AC
影响因子：
4.4
作者：
Meyer-Siegler, Katherine L.;Iczkowski, Kenneth A.;Vera, Pedro L.
通讯作者：
Vera, Pedro L.
DOI：
10.1164/rccm.201110-1864oc
发表时间：
2012-07-15
影响因子：
24.7
作者：
Adamali, Huzaifa;Armstrong, Michelle E.;Donnelly, Seamas C.
通讯作者：
Donnelly, Seamas C.