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Updated: Apr 15, 2026
Detection of a Circulating MicroRNA Custom Panel in Patients with Metastatic Colorectal Cancer
Published on: March 14, 2019
C/EBP-β-activated microRNA-223 promotes tumour growth through targeting RASA1 in human colorectal cancer
1State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, People's Republic of China.
Background:
Evidences have shown that the RAS signalling pathway plays an important role in colorectal cancer (CRC). Moreover, RAS-GTPase-activating proteins (RASGAPs) as RAS signalling terminators are associated with tumourigenicity and tumour progression. In this study, we used bioinformatics analysis to predict and study important miRNAs that could target RAS p21 GTPase-activating protein 1 (RASA1), an important member of RASGAPs.
Methods:
The levels of RASA1 and miR-223 were analysed by real-time PCR, western blotting or in situ immunofluorescence analyses. The functional effects of miR-223 and the effects of miR-223-targeted inhibitors were examined in vivo using established assays.
Results:
Upregulation of miR-223 was detected in CRC tissues (P<0.01) and was involved in downregulation of RASA1 in CRC tissues. Furthermore, the direct inhibition of RASA1 translation by miR-223 and the activation of miR-223 by CCAAT/enhancer binding protein-β (C/EBP-β) were evaluated in CRC cells. An in vivo xenograft model of CRC suggested that the upregulation of miR-223 could promote tumour growth and that the inhibition of miR-223 might prevent solid tumour growth.
Conclusions:
These results identify that C/EBP-β-activated miR-223 contributes to tumour growth by targeting RASA1 in CRC and miR-223-targeted inhibitors may have clinical promise for CRC treatment via suppression of miR-223.
Insights
MicroRNA-223 (miR-223) promotes colorectal cancer (CRC) growth by targeting RASA1. Inhibiting miR-223 shows promise for CRC treatment by suppressing tumor growth.
Area of Science:
- Oncology
- Molecular Biology
- Bioinformatics
Background:
- The RAS signaling pathway is crucial in colorectal cancer (CRC) development.
- RAS-GTPase-activating proteins (RASGAPs) regulate RAS signaling and are linked to tumor progression.
- RAS p21 GTPase-activating protein 1 (RASA1) is a key RASGAP implicated in cancer.
Purpose of the Study:
- To investigate the role of microRNAs (miRNAs) targeting RASA1 in colorectal cancer.
- To identify specific miRNAs involved in CRC pathogenesis through bioinformatics analysis.
Main Methods:
- Real-time PCR and western blotting to quantify RASA1 and miR-223 levels.
- In situ immunofluorescence for protein localization.
- In vivo xenograft models to assess functional effects of miR-223 and inhibitors.
Main Results:
- miR-223 was upregulated in CRC tissues, correlating with RASA1 downregulation.
- miR-223 directly inhibits RASA1 translation and is activated by C/EBP-β.
- Upregulated miR-223 promoted tumor growth in vivo; miR-223 inhibition reduced tumor growth.
Conclusions:
- C/EBP-β-activated miR-223 drives CRC tumor growth by targeting RASA1.
- miR-223-targeted inhibitors represent a potential therapeutic strategy for colorectal cancer.
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