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Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
MicroRNA-200 is commonly repressed in conjunctival MALT lymphoma, and targets cyclin E2
Jiping Cai1, Xiaoyu Liu, Jinwei Cheng
1Department of Ophthalmology of Shanghai Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai, 200003, People's Republic of China.
Background:
Aberrant microRNA expression is implicated in cancer initiation and progression. We sought to identify dysregulated miRNAs in conjunctival mucosa-associated lymphoid tissue (MALT) lymphoma, and investigated their biological significance.
Methods:
The profiles of miRNAs in conjunctival MALT lymphoma and normal adjacent tissues were investigated by microRNA microarray of four pairs of surgically removed conjunctival MALT lymphoma tissues and matched controls. The results of microarray were further confirmed in 14 paired conjunctival MALT lymphoma samples (including the former four pairs) using quantitative RT-PCR. The functional effect of miR-200 was examined further. A luciferase reporter assay was performed to confirm the predicted target.
Results:
The microarray results revealed upregulated miR-150/155, and downregulated miR-184, miR-200a, b, c, and miR-205. These findings were confirmed by quantitative RT-PCR. Targetscan analysis suggested cyclin E2 as potential target of miR-200a, b, c. Luciferase reporter assay using vectors containing the 3'UTR of cyclin E2 showed that miR-200a, b, c could suppress luciferase activities. RT-PCR and immunoblotting studies revealed that overexpression of miR-200a, b, c reduced the mRNA and protein levels of cyclin E2 respectively.
Conclusions:
We demonstrated that miRNAs were dysregulated in conjunctival MALT lymphoma, and dysregulation of the miR-200 family could be involved in the pathogenesis and progression of the disease.
Insights
Dysregulated microRNAs (miRNAs) were identified in conjunctival mucosa-associated lymphoid tissue (MALT) lymphoma. The miR-200 family
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Aberrant microRNA (miRNA) expression is a known factor in cancer development.
- This study focuses on identifying specific miRNA alterations in conjunctival mucosa-associated lymphoid tissue (MALT) lymphoma.
- The biological roles of these dysregulated miRNAs in the disease are explored.
Purpose of the Study:
- To identify differentially expressed miRNAs in conjunctival MALT lymphoma compared to normal tissues.
- To investigate the functional significance of identified miRNAs, particularly the miR-200 family.
- To elucidate the role of miRNA dysregulation in the pathogenesis of conjunctival MALT lymphoma.
Main Methods:
- MicroRNA microarray analysis of conjunctival MALT lymphoma and adjacent normal tissues.
- Quantitative reverse transcription-polymerase chain reaction (RT-PCR) for validation.
- Luciferase reporter assays and immunoblotting to confirm target interactions and effects.
Main Results:
- Microarray analysis revealed upregulation of miR-150/155 and downregulation of miR-184, miR-200a/b/c, and miR-205.
- Quantitative RT-PCR confirmed these expression patterns.
- The miR-200 family (miR-200a, b, c) was shown to target and suppress cyclin E2 expression at both mRNA and protein levels.
Conclusions:
- MicroRNAs are significantly dysregulated in conjunctival MALT lymphoma.
- The miR-200 family's downregulation and its targeting of cyclin E2 suggest a role in the disease's pathogenesis and progression.
- These findings highlight potential miRNA-based biomarkers or therapeutic targets for conjunctival MALT lymphoma.
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