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Published on: March 30, 2019
MicroRNA 133A Regulates Cell Proliferation, Cell Migration, and Apoptosis in Colorectal Cancer by Suppressing CDH3
Grinsun Sharma1, Ji-Su Mo2, Santosh Lamichhane1
1Department of Pathology, School of Medicine, Wonkwang University, Iksan, Chonbuk 54538, Republic of Korea.
Abstract:
MicroRNAs are endogenous, non-coding RNA that play an essential role in colorectal carcinoma (CRC) pathogenesis by targeting specific genes. This research aimed to determine and validate the target genes of the MIR133A associated with CRC. We verified that cadherin 3 (CDH3) is the direct target gene of MIR133A using a luciferase reporter assay, quantitative RT-PCR, and western blot analyses. CDH3 mRNA and protein expression were reduced significantly in CRC cells after transfection with MIR133A or siCDH3. We also verified that MIR133A regulated CDH3-mediated catenin, matrix metalloproteinase, apoptosis, and the epithelial-mesenchymal transition (EMT) pathway. Knockdown of CDH3 in CRC cell lines by siCDH3 produced similar results. Compared with adjacent non-tumor tissues, CDH3 protein expression was upregulated in CRC tissues, which is further confirmed by immunohistochemistry. Additionally, molecular and functional studies revealed that cell viability, migration, and colony formation were significantly reduced, and apoptosis was increased in CRC cell lines transfected with MIR133A or siCDH3. Our results suggest that MIR133A regulates CDH3 expression in human CRC.
Insights
MicroRNA-133a (MIR133A) directly targets Cadherin 3 (CDH3) in colorectal cancer. This interaction suppresses tumor growth and metastasis by regulating key cellular pathways.
Area of Science:
- Molecular Biology
- Genetics
- Oncology
Background:
- MicroRNAs are crucial regulators in cancer development.
- Colorectal carcinoma (CRC) pathogenesis involves complex gene regulation.
- Identifying microRNA targets is key to understanding cancer mechanisms.
Purpose of the Study:
- To identify and validate direct target genes of MIR133A in colorectal cancer.
- To elucidate the functional role of the MIR133A-CDH3 interaction in CRC.
- To investigate the impact of this interaction on cancer cell behavior.
Main Methods:
- Luciferase reporter assays to confirm direct targeting.
- Quantitative RT-PCR and Western blot to assess gene and protein expression.
- Transfection with MIR133A mimics and CDH3 siRNAs in CRC cell lines.
- Immunohistochemistry to evaluate CDH3 expression in tumor tissues.
Main Results:
- Cadherin 3 (CDH3) was confirmed as a direct target of MIR133A.
- MIR133A transfection significantly reduced CDH3 mRNA and protein levels in CRC cells.
- CDH3 knockdown mimicked the effects of MIR133A, reducing cell viability, migration, and colony formation while increasing apoptosis.
- CDH3 protein expression was upregulated in CRC tissues compared to adjacent non-tumor tissues.
- MIR133A regulated pathways including catenin, matrix metalloproteinase, apoptosis, and epithelial-mesenchymal transition (EMT).
Conclusions:
- MIR133A directly targets and downregulates CDH3 expression in human colorectal cancer.
- The MIR133A-CDH3 axis plays a significant role in regulating CRC cell proliferation, migration, and apoptosis.
- MIR133A acts as a tumor suppressor in CRC by inhibiting CDH3-mediated pathways.
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