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Investigation of the role and mechanism of ARHGAP5-mediated colorectal cancer metastasis
- Source :
- Theranostics
- Publication Year :
- 2020
- Publisher :
- Ivyspring International Publisher, 2020.
-
Abstract
- Background: Metastatic colorectal cancer (CRC) is a lethal disease; however, the underlying molecular mechanisms remain unclear and require further study. Methods: RNA-Seq, PCR, Western blotting, immunohistochemistry, ChIP and RNAi assays were performed to investigate Rho GTPase-activating protein 5 (ARHGAP5, aslo known as p190RhoGAP-B, p190-B) expression and the clinical relevance, functional roles and regulatory mechanisms of this protein using human CRC cells and tissues. In vivo, two cell-based xenograft models were used to evaluate the roles of ARHGAP5 in CRC metastasis. Results: Here, we report that ARHGAP5 expression is significantly increased in metastatic CRC tissues and is inversely associated with patient overall survival. The suppression of ARHGAP5 reduces CRC cell metastasis in vitro and in cell-based xenograft models. Furthermore, we show that ARHGAP5 promotes CRC cell epithelial-mesenchymal transition by negatively regulating RhoA activity. Mechanistically, cAMP response element-binding protein (CREB1) transcriptionally upregulates ARHGAP5 expression, and decreased miR-137 further contributes to ARHGAP5 mRNA stability in CRC. Conclusions: Overall, our study highlights the crucial function of ARHGAP5 in CRC metastasis, thus suggesting novel prognostic biomarkers and hypothetical therapeutic targets.
- Subjects :
- 0301 basic medicine
ARHGAP5
Epithelial-Mesenchymal Transition
RHOA
Colorectal cancer
Cell
Mice, Nude
Medicine (miscellaneous)
colorectal cancer
miR-137
Cell Line
Metastasis
03 medical and health sciences
0302 clinical medicine
Cell Movement
RNA interference
Cell Line, Tumor
Animals
Humans
Medicine
RNA, Messenger
Neoplasm Metastasis
Cyclic AMP Response Element-Binding Protein
Pharmacology, Toxicology and Pharmaceutics (miscellaneous)
Mice, Inbred BALB C
tumor metastasis
biology
business.industry
GTPase-Activating Proteins
medicine.disease
digestive system diseases
Up-Regulation
Gene Expression Regulation, Neoplastic
MicroRNAs
mir-137
HEK293 Cells
030104 developmental biology
medicine.anatomical_structure
030220 oncology & carcinogenesis
biology.protein
Cancer research
CREB1
Immunohistochemistry
Female
Colorectal Neoplasms
rhoA GTP-Binding Protein
business
Research Paper
Subjects
Details
- ISSN :
- 18387640
- Volume :
- 10
- Database :
- OpenAIRE
- Journal :
- Theranostics
- Accession number :
- edsair.doi.dedup.....334fea7ccdaac4700b4efc80dac04831