Knockdown of CSE1L Gene in Colorectal Cancer Reduces Tumorigenesis in Vitro
Knockdown of CSE1L Gene in Colorectal Cancer Reduces Tumorigenesis in Vitro
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DOI：
10.1016/j.ajpath.2016.06.016
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发表时间：
2016-10-01
影响因子：
6
通讯作者：
Malafa, Mokenge P.
中科院分区：
文献类型：
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作者：
Pimiento, Jose M.;Neill, Kevin G.;Malafa, Mokenge P.
人类细胞凋亡易感性基因（chromosomal segregation 1-like，CSE 1 L）在有丝分裂、细胞增殖和凋亡过程中的核质转运和染色体分离中发挥作用。CSE 1 L参与结肠癌的发生。使用Affyphase U133 +基因芯片，用三个数据集在正常人结肠粘膜（NR）、腺瘤（AD）和结直肠癌（CRC）上评估CSEIL基因表达。使用组织芯片通过免疫组织化学测量来自相同患者的CRC、AD和NR中的CSE 1 L蛋白表达。我们评估了CSE 1 L在CRC细胞（HCT 116、SW 480和HT 29）中的表达及其生物学功能。CSE 1 L mRNA在AD和CRC中的表达均显著高于NR（P < 0.001和P = 0.02）。我们通过免疫组化观察到CSE 1 L染色强度和细胞定位的变化。在CRC组织微阵列中，与NR相比，CSE 1 L在AD向CRC转变期间显著增加（P = 0.01和P < 0.001）。HCT 116、SW 480和HT 29细胞也表达CSE 1 L蛋白。通过shRNA敲低CSE 1 L抑制蛋白，导致细胞增殖减少，软琼脂中集落形成减少，并诱导凋亡。CSE 1 L蛋白在CRC发展的早期和所有阶段表达。CSE 1 L的shRNA敲低与CRC细胞中肿瘤发生的抑制相关。CSE 1 L可能是治疗CRC的潜在靶点。
Human cellular apoptosis susceptibility (chromosomal segregation 1-like, CSE1L) gene plays a role in nuclear-to-cytoplasm transport and chromosome segregation during mitosis, cellular proliferation, and apoptosis. CSE1L is involved in colon carcinogenesis. CSEIL gene expression was assessed with three data sets using Affymetrix U133 + gene chips on normal human colonic mucosa (NR), adenomas (ADs), and colorectal carcinoma (CRC). CSE1L protein expression in CRC, AD, and NR from the same patients was measured by immunohistochemistry using a tissue microarray. We evaluated CSE1L expression in CRC cells (HCT116, SW480, and HT29) and its biological functions. CSE1L mRNA was significantly increased in all AD and CRC compared with NR (P < 0.001 and P = 0.02, respectivly). We observed a change in CSE1L staining intensity and cellular localization by immunohistochemistry. CSE1L was significantly increased during the transition from AD to CRC when compared with NR in a CRC tissue microarray (P = 0.01 and P < 0.001). HCT116, SW480, and HT29 cells also expressed CSE1L protein. CSE1L knockdown by shRNA inhibited protein, resulting in decreased cell proliferation, reduced colony formation in soft agar, and induction of apoptosis. CSE1L protein is expressed early and across all stages of CRC development. shRNA knockdown of CSE1L was associated with inhibition of tumorigenesis in CRC cells. CSE1L may represent a potential target for treatment of CRC.