Over-expression of AURKA, SKA3 and DSN1 contributes to colorectal adenoma to carcinoma progression.

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.

• Authors: Tzu-Po Chuang, Jaw-Yuan Wang, Shu-Wen Jao, Chang-Chieh Wu, Jiann-Hwa Chen, Koung-Hung Hsiao, Chung-Yen Lin, Shu-Hwa Chen, Sheng-Yao Su, Ying-Ju Chen, Yuan-Tsong Chen, Deng-Chyang Wu, Ling-Hui Li
• Journal: Oncotarget (Oncotarget) Vol. 7 Issue 29 Pg. 45803-45818 (Jul 19 2016) ISSN: 1949-2553 [Electronic] United States
• PMID: 27329586 (Publication Type: Journal Article)

Chemical References

• Cell Cycle Proteins
• Chromosomal Proteins, Non-Histone
• DSN1 protein, human
• Microtubule-Associated Proteins
• Ska3 protein, human
• AURKA protein, human
• Aurora Kinase A

Topics

• Adenocarcinoma (genetics, pathology)
• Adenoma (genetics, pathology)
• Adult
• Aged
• Area Under Curve
• Aurora Kinase A (biosynthesis)
• Cell Cycle Proteins
• Cell Transformation, Neoplastic (genetics)
• Chromosomal Proteins, Non-Histone (biosynthesis)
• Colorectal Neoplasms (genetics, pathology)
• Disease Progression
• Female
• Gene Expression Profiling
• Humans
• Male
• Microtubule-Associated Proteins (biosynthesis)
• Middle Aged
• ROC Curve
• Transcriptome
• Up-Regulation