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Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome
Published on: June 15, 2016
Downregulation of microRNAs-143 and -145 in B-cell malignancies
Yukihiro Akao1, Yoshihito Nakagawa, Yukio Kitade
1Department of Medical Oncology, Gifu International Institute of Biotechnology, 1-1 Naka-Fudogaoka, Kakamigahara, Gifu 504-0838, Japan. yakao@giib.or.jp
Abstract:
Recently, it has been found that inappropriate expression of microRNAs (miRNAs) is strongly associated with carcinogenesis. In this study, we demonstrated that the expression of miRNAs (miRs) -143 and -145, the levels of which were previously shown to be reduced in colon cancers and various kinds of established cancer cell lines, was also decreased in most of the B-cell malignancies examined, including chronic lymphocytic leukemias (CLL), B-cell lymphomas, Epstein-Barr virus (EBV)-transformed B-cell lines, and Burkitt lymphoma cell lines. All samples from 13 CLL patients and eight of nine B-cell lymphoma ones tested exhibited an extremely low expression of miRs-143 and -145. The expression levels of miRs-143 and -145 were consistently low in human Burkitt lymphoma cell lines and were inversely associated with the cell proliferation observed in the EBV-transformed B-cell lines. Moreover, the introduction of either precursor or mature miR-143 and -145 into Raji cells resulted in a significant growth inhibition that occurred in a dose-dependent manner and the target gene of miRNA-143 was determined to be ERK5, as previously reported in human colon cancer DLD-1 cells. Taken together, these findings suggest that miRs-143 and -145 may be useful as biomarkers that differentiate B-cell malignant cells from normal cells and contribute to carcinogenesis in B-cell malignancies by a newly defined mechanism.
Insights
Reduced expression of microRNAs (miRNAs) -143 and -145 is linked to B-cell malignancies. Restoring these miRNAs inhibited cancer cell growth, suggesting their potential as biomarkers for B-cell cancers.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- MicroRNA (miRNA) dysregulation is implicated in cancer development.
- Previous studies indicated reduced miR-143 and miR-145 in colon cancer.
- These miRNAs are known tumor suppressors in various cancers.
Purpose of the Study:
- To investigate the expression of miR-143 and miR-145 in B-cell malignancies.
- To determine the role of miR-143 and miR-145 in B-cell cancer proliferation.
- To explore the potential of miR-143 and miR-145 as diagnostic biomarkers.
Main Methods:
- Quantitative real-time PCR to measure miRNA expression in patient samples and cell lines.
- Transfection of miRNA precursors and mature forms into B-cell lines (Raji cells).
- Cell proliferation assays and Western blot analysis to identify target genes.
Main Results:
- miR-143 and miR-145 expression was significantly decreased in chronic lymphocytic leukemias (CLL), B-cell lymphomas, and Burkitt lymphoma cell lines.
- Low miR-143/miR-145 levels correlated with increased proliferation in Epstein-Barr virus (EBV)-transformed B-cell lines.
- Introduction of miR-143/miR-145 suppressed B-cell malignancy cell growth in a dose-dependent manner.
- ERK5 was identified as a target gene of miR-143.
Conclusions:
- miR-143 and miR-145 are frequently downregulated in B-cell malignancies.
- These miRNAs may act as tumor suppressors in B-cell cancers by inhibiting cell proliferation.
- miR-143 and miR-145 show promise as biomarkers for differentiating malignant B-cells from normal cells.
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