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The function of BTG3 in colorectal cancer cells and its possible signaling pathway
- Source :
- Journal of Cancer Research and Clinical Oncology
- Publication Year :
- 2017
- Publisher :
- Springer Science and Business Media LLC, 2017.
-
Abstract
- Purpose B-cell translocation gene 3 (BTG3) has been identified as a candidate driver gene for various cancers, but its specific role in colorectal cancer (CRC) is poorly understood. We aimed to investigate the relationship between expression of BTG3 and clinicopathological features and prognosis, as well as to explore the effects and the role of a possible BTG3 molecular mechanism on aggressive colorectal cancer behavior. Methods BTG3 expression was assessed by immunohistochemistry (IHC) on specimens from 140 patients with CRC. The association of BTG3 expression with clinicopathological features was examined. To confirm the biological role of BTG3 in CRC, two CRC cell lines expressing BTG3 were used and BTG3 expression was knocked down by shRNA. CCK-8, cell cycle, apoptosis, migration, and invasion assays were performed. The influence of BTG3 knockdown was further investigated by genomic microarray to uncover the potential molecular mechanisms underlying BTG3-mediated CRC development and progression. Results BTG3 was downregulated in colorectal cancer tissues and positively correlated with pathological classification (p = 0.037), depth of invasion (p = 0.016), distant metastasis (p = 0.024), TNM stage (p = 0.007), and overall survival (OS) and disease-free survival (DFS). BTG3 knockdown promoted cell proliferation, migration, invasion, relieved G2 arrest, and inhibited apoptosis in HCT116 and LoVo cells. A genomic microarray analysis showed that numerous tumor-associated signaling pathways and oncogenes were altered by BTG3 knockdown. At the mRNA level, nine genes referred to the extracellular-regulated kinase/mitogen-activated protein kinase pathway were differentially expressed. Western blotting revealed that BTG3 knockdown upregulated PAK2, RPS6KA5, YWHAB, and signal transducer and activator of transcription (STAT)3 protein levels, but downregulated RAP1A, DUSP6, and STAT1 protein expression, which was consistent with the genomic microarray data. Conclusions BTG3 expression might contribute to CRC carcinogenesis. BTG3 knockdown might strengthen the aggressive colorectal cancer behavior.
- Subjects :
- Male
0301 basic medicine
Cancer Research
Microarray
Colorectal cancer
Down-Regulation
Cell Cycle Proteins
medicine.disease_cause
03 medical and health sciences
0302 clinical medicine
Cell Movement
Cell Line, Tumor
BTG3
Tumor Cells, Cultured
medicine
Humans
STAT1
Cell Proliferation
Gene knockdown
Paraffin Embedding
biology
Microarray analysis techniques
Proteins
General Medicine
Biological behavior
Middle Aged
Cell cycle
Prognosis
HCT116 Cells
medicine.disease
Immunohistochemistry
030104 developmental biology
Oncology
Genomic microarray
Gene Knockdown Techniques
030220 oncology & carcinogenesis
biology.protein
Cancer research
Female
Signal transduction
Original Article – Cancer Research
Colorectal Neoplasms
Carcinogenesis
HT29 Cells
Signal Transduction
Subjects
Details
- ISSN :
- 14321335 and 01715216
- Volume :
- 144
- Database :
- OpenAIRE
- Journal :
- Journal of Cancer Research and Clinical Oncology
- Accession number :
- edsair.doi.dedup.....b28795eed77131fe153e38fd4f09e6b6