Over-expression of AURKA, SKA3 and DSN1 contributes to colorectal adenoma to carcinoma progression.
Over-expression of AURKA, SKA3 and DSN1 contributes to colorectal adenoma to carcinoma progression.
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DOI：
10.18632/oncotarget.9960
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发表时间：
2016-07-19
期刊：
影响因子：
--
通讯作者：
Li LH
中科院分区：
文献类型：
--
作者：
Chuang TP;Wang JY;Jao SW;Wu CC;Chen JH;Hsiao KH;Lin CY;Chen SH;Su SY;Chen YJ;Chen YT;Wu DC;Li LH
结直肠癌（CRC）的发展涉及正常粘膜组织连续转化为良性腺瘤，然后腺瘤转化为恶性肿瘤。大肠腺瘤（CRA）恶性转化的关键基因的鉴定主要是基于横断面观察。在这项研究中，我们使用自体样本鉴定了相关基因。通过对个体患者的腺癌、腺瘤性息肉和非肿瘤性结肠组织（称为三部分样本）进行全基因组SNP基因分型和RNA测序分析，我们鉴定了68个具有差异拷贝数改变和进行性表达失调的基因。Aurora A、SKA 3和DSN 1蛋白水平在样品中依次上调，并且这种过表达与染色体不稳定性（CIN）相关。CRC细胞中SKA 3的敲低显著降低细胞生长速率并增加细胞凋亡。SKA 3或DSN 1的耗竭诱导G2/M期阻滞，并降低迁移、侵袭和锚定非依赖性生长。因此，AURKA和DSN 1对CRA中染色体20 q扩增相关的恶性转化至关重要。此外，染色体13 q上的SKA 3被鉴定为参与促进恶性转化的新基因。评估这些基因的表达可能有助于识别进行性腺瘤患者，有助于改善治疗。
Development of colorectal cancer (CRC) involves sequential transformation of normal mucosal tissues into benign adenomas and then adenomas into malignant tumors. The identification of genes crucial for malignant transformation in colorectal adenomas (CRAs) has been based primarily on cross-sectional observations. In this study, we identified relevant genes using autologous samples. By performing genome-wide SNP genotyping and RNA sequencing analysis of adenocarcinomas, adenomatous polyps, and non-neoplastic colon tissues (referred as tri-part samples) from individual patients, we identified 68 genes with differential copy number alterations and progressively dysregulated expression. Aurora A, SKA3, and DSN1 protein levels were sequentially up-regulated in the samples, and this overexpression was associated with chromosome instability (CIN). Knockdown of SKA3 in CRC cells dramatically reduced cell growth rates and increased apoptosis. Depletion of SKA3 or DSN1 induced G2/M arrest and decreased migration, invasion, and anchorage-independent growth. AURKA and DSN1 are thus critical for chromosome 20q amplification-associated malignant transformation in CRA. Moreover, SKA3 at chromosome 13q was identified as a novel gene involved in promoting malignant transformation. Evaluating the expression of these genes may help identify patients with progressive adenomas, helping to improve treatment.
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影响因子：
29.4
作者：
Boland CR;Goel A
通讯作者：
Goel A
DOI：
10.1158/1940-6207.capr-12-0484
发表时间：
2013-07
期刊：
Cancer prevention research (Philadelphia, Pa.)
影响因子：
--
作者：
Broussard EK;Kim R;Wiley JC;Marquez JP;Annis JE;Pritchard D;Disis ML
通讯作者：
Disis ML
影响因子：
8
作者：
Lin, YM;Furukawa, Y;Nakamura, Y
通讯作者：
Nakamura, Y
影响因子：
24.5
作者：
Citarda, F;Tomaselli, G;Crespi, M
通讯作者：
Crespi, M
影响因子：
3.8
作者：
Maglietta, Rosalia;Liuzzi, Vania Cosma;Ancona, Nicola
通讯作者：
Ancona, Nicola