1. Over-expression of AURKA, SKA3 and DSN1 contributes to colorectal adenoma to carcinoma progression
- Author
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Sheng Yao Su, Yuan-Tsong Chen, Ying Ju Chen, Chung Yen Lin, Chang Chieh Wu, Shu Wen Jao, Jiann Hwa Chen, Koung Hung Hsiao, Tzu Po Chuang, Shu Hwa Chen, Jaw-Yuan Wang, Ling-Hui Li, and Deng-Chyang Wu
- Subjects
Adenoma ,Adult ,Male ,0301 basic medicine ,malignant transformation ,Chromosomal Proteins, Non-Histone ,Colorectal cancer ,colon cancer progression ,Cell Cycle Proteins ,DSN1 ,Colorectal adenoma ,Adenocarcinoma ,SKA3 ,Malignant transformation ,03 medical and health sciences ,0302 clinical medicine ,Chromosome instability ,Carcinoma ,Humans ,Medicine ,Aged ,Aurora Kinase A ,AURKA ,Gene knockdown ,business.industry ,Gene Expression Profiling ,Middle Aged ,medicine.disease ,Up-Regulation ,Cell Transformation, Neoplastic ,030104 developmental biology ,ROC Curve ,Oncology ,Area Under Curve ,030220 oncology & carcinogenesis ,Disease Progression ,Cancer research ,Female ,Colorectal Neoplasms ,Transcriptome ,business ,Microtubule-Associated Proteins ,Research Paper - Abstract
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.
- Published
- 2016