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Detection of a Circulating MicroRNA Custom Panel in Patients with Metastatic Colorectal Cancer
Published on: March 14, 2019
MicroRNA-383 acts as a tumor suppressor in colorectal cancer by modulating CREPT/RPRD1B expression
Jian Li1, Amber R Smith2, Rebecca T Marquez2
1School of Environmental and Chemical Engineering, Yanshan University, Qinhuangdao, Hebei Province, China.
Abstract:
CREPT (Cell-cycle-related and expression-elevated protein in tumor)/RPRD1B, a novel protein that enhances the transcription of Cyclin D1 to promote cell proliferation during tumorigenesis, was demonstrated highly expressed in most of tumors. However, it remains unclear how CREPT is regulated in colorectal cancers. In this study, we report that miR-383 negatively regulates CREPT expression. We observed that CREPT was up-regulated but the expression of miR-383 was down regulated in both colon cancer cell lines and colon tumor tissues. Intriguingly, we found that enforced expression of miR-383 inhibited the expression of CREPT at both the mRNA and protein level. Using a luciferase reporter, we showed that miR-383 targeted the 3'-UTR of CREPT mRNA directly. Consistently we observed that over expression of miR-383 shortened the half-life of CREPT mRNA in varieties of colorectal cancer cells. Furthermore, restoration of miR-383 inhibited cell growth and colony formation of colon cancer cells accompanied by inhibition of expression of CREPT and related downstream genes. Finally, we demonstrated that stable over expression of miR-383 in colon cancer cells decreased the growth of the tumors. Our results revealed that the abundant expression of CREPT in colorectal cancers is attributed to the decreased level of miR-383. This study shed a new light on the potential therapeutic therapy strategy for colorectal cancers using introduced miRNA.
Insights
MicroRNA-383 (miR-383) suppresses colorectal cancer growth by inhibiting Cell-cycle-related and expression-elevated protein in tumor (CREPT) expression. Decreased miR-383 levels contribute to high CREPT expression in tumors, suggesting miRNA-based therapies.
Area of Science:
- Molecular Biology
- Oncology
- Gene Regulation
Background:
- Cell-cycle-related and expression-elevated protein in tumor (CREPT) promotes cell proliferation and is highly expressed in various tumors.
- The regulatory mechanisms of CREPT in colorectal cancer (CRC) remain largely unknown.
- MicroRNAs (miRNAs) are critical regulators of gene expression implicated in cancer development.
Purpose of the Study:
- To investigate the role of miR-383 in regulating CREPT expression in colorectal cancer.
- To elucidate the functional consequences of miR-383/CREPT interaction on CRC cell behavior and tumor growth.
Main Methods:
- Quantitative real-time PCR and Western blotting to assess CREPT and miR-383 expression levels.
- Luciferase reporter assays to confirm direct targeting of CREPT by miR-383.
- Cell proliferation, colony formation, and in vivo tumor growth assays in response to miR-383 modulation.
Main Results:
- CREPT was upregulated, while miR-383 was downregulated in CRC cell lines and tissues.
- miR-383 directly targeted the 3'-UTR of CREPT mRNA, inhibiting its expression at both mRNA and protein levels.
- Overexpression of miR-383 suppressed CRC cell proliferation, colony formation, and tumor growth, accompanied by decreased CREPT levels.
Conclusions:
- The study identifies miR-383 as a negative regulator of CREPT in colorectal cancer.
- Decreased miR-383 levels contribute to the aberrant overexpression of CREPT in CRC.
- miR-383 represents a potential therapeutic target for colorectal cancer treatment.
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