Downregulation of stathmin 1 in human gallbladder carcinoma inhibits tumor growth in vitro and in vivo.
Downregulation of stathmin 1 in human gallbladder carcinoma inhibits tumor growth in vitro and in vivo.
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人胆囊癌中 Stathmin 1 的下调可抑制体外和体内肿瘤生长
DOI：
10.1038/srep28833
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发表时间：
2016-06-28
影响因子：
4.6
通讯作者：
Liu H
中科院分区：
文献类型：
--
作者：
Wang J;Yao Y;Ming Y;Shen S;Wu N;Liu J;Liu H;Suo T;Pan H;Zhang D;Ding K;Liu H
胆囊癌是一种高致死性的胃肠道恶性肿瘤。尽管有广泛的研究，GBC的潜在分子机制仍不清楚。Stathmin 1（STMN 1）是一种与微管稳定性相关的重要胞浆蛋白，据报道其参与肿瘤发生。但就我们所知，其在胆囊癌中的作用尚未被分析。在这项研究中，我们发现STMN 1显着高表达GBC的免疫组织化学（IHC）。进一步的研究表明，沉默STMN 1抑制体外细胞生长。此外，STMN 1的敲除可诱导GBC细胞凋亡并延迟G2/M期转化。我们的研究结果为进一步研究STMN 1基因沉默可能调控p38 MAPK激酶和p53/p21信号通路的活性提供了理论依据。此外，在体内沉默STMN 1后，异种移植胆囊癌细胞的生长显著受损。这些结果表明，STMN 1在细胞增殖和迁移中起重要作用。这为探讨胆囊癌的治疗靶点提供了潜在的线索。
Gallbladder carcinoma (GBC) is a highly lethal malignancy of the gastrointestinal tract. Despite extensive research, the underlying molecular mechanism of GBC remains largely unclear. Stathmin 1 (STMN1) is an important cytosolic protein associated with microtubule stability that was reported to be involved in tumorigenesis. Up to our knowledge, its role in gallbladder carcinoma has not been analyzed. In this study, we found that STMN1 was significantly highly expressed in GBC by immunohistochemistry (IHC). Further research demonstrated that silencing of STMN1 inhibited cell growth in vitro. Moreover, knockdown of STMN1 induced apoptosis and delayed G2/M phase transformation in GBC cells. Our data support a rationale for further studies that the silencing of STMN1 may regulate the activity of p38 MAPK kinase and p53/p21 signal pathway. Besides, xenografted gallbladder carcinoma cells growth were significantly impaired after STMN1 was silenced in vivo. These results suggested that STMN1 played an important role in cell proliferation and migration. This provided a potential clue for investigating the therapeutic target in GBC.