Back to Search
Start Over
Over-expression of AURKA, SKA3 and DSN1 contributes to colorectal adenoma to carcinoma progression
- Source :
- Oncotarget
- Publication Year :
- 2016
- Publisher :
- Impact Journals, LLC, 2016.
-
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.
- 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
Subjects
Details
- ISSN :
- 19492553
- Volume :
- 7
- Database :
- OpenAIRE
- Journal :
- Oncotarget
- Accession number :
- edsair.doi.dedup.....433956d99e1beeba64183ce14e24f343