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

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

Research output: Contribution to journalArticle

25 Citations (Scopus)

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 genomewide 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.

Original languageEnglish
Pages (from-to)45803-45818
Number of pages16
JournalOncotarget
Volume7
Issue number29
DOIs
Publication statusPublished - Jan 1 2016
Externally publishedYes

Keywords

  • AURKA
  • Colon cancer progression
  • DSN1
  • Malignant transformation
  • SKA3

ASJC Scopus subject areas

  • Oncology

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  • Cite this

    Chuang, T. P., Wang, J. Y., Jao, S. W., Wu, C. C., Chen, J. H., Hsiao, K. H., Lin, C. Y., Chen, S. H., Su, S. Y., Chen, Y. J., Chen, Y. T., Wu, D. C., & Li, L. H. (2016). Over-expression of AURKA, SKA3 and DSN1 contributes to colorectal adenoma to carcinoma progression. Oncotarget, 7(29), 45803-45818. https://doi.org/10.18632/oncotarget.9960