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

Autor:	Chuang TP; Taiwan International Graduate Program in Molecular Medicine, National Yang-Ming University and Academia Sinica, Taipei, Taiwan.; Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan.; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan., Wang JY; Division of Gastroenterology and General Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.; Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.; Center for Biomarkers and Biotech Drugs, Kaohsiung Medical University, Kaohsiung, Taiwan., Jao SW; Department of Surgery, Division of Colon and Rectal Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan., Wu CC; Department of Surgery, Division of Colon and Rectal Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan., Chen JH; Department of Internal Medicine, Tzu Chi General Hospital, Taipei Branch, Taipei, Taiwan., Hsiao KH; Department of Colorectal Surgery, Tzu Chi General Hospital, Taipei Branch, Taipei, Taiwan., Lin CY; Institute of Information Science, Academia Sinica, Taipei, Taiwan., Chen SH; Institute of Information Science, Academia Sinica, Taipei, Taiwan., Su SY; Institute of Information Science, Academia Sinica, Taipei, Taiwan., Chen YJ; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan., Chen YT; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan., Wu DC; Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.; Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan.; Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan., Li LH; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
Jazyk:	angličtina
Zdroj:	Oncotarget [Oncotarget] 2016 Jul 19; Vol. 7 (29), pp. 45803-45818.
DOI:	10.18632/oncotarget.9960
Abstrakt:	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. Competing Interests: The authors declare no conflicts of interest.
Databáze:	MEDLINE
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