Dysregulation of the mitogen granulin in human cancer through the miR-15/107 microRNA gene group
Abstract
Granulin (GRN) is a potent mitogen and growth factor implicated in many human cancers, but its regulation is poorly understood. Recent findings indicate that GRN is regulated strongly by the microRNA miR-107, which functionally overlaps with miR-15, miR-16, and miR-195 due to a common 5′ sequence critical for target specificity. In this study, we queried whether miR-107 and paralogs regulated GRN in human cancers. In cultured cells, anti-argonaute RNA coimmunoprecipitation with downstream microarray analyses indicates that GRN mRNA is directly targeted by numerous miR-15/107 miRNAs. We further tested this association in human tumors. MiR-15 and miR-16 are known to be downregulated in chronic lymphocytic leukemia (CLL). Using pre-existing microarray datasets, we found that GRN expression is higher in CLL relative to nonneoplastic lymphocytes (P < 0.00001). By contrast, other prospective miR-15/miR-16 targets in the dataset (BCL-2 and cyclin D1) were not upregulated in CLL. Unlike in CLL, GRN was not upregulated in chronic myelogenous leukemia (CML) where miR-107 paralogs are not known to be dysregulated. Prior studies have shown that GRN is also upregulated, and miR-107 downregulated, in prostate carcinoma. Our results indicate that multiple members of the miR-107 gene group indeed repress GRN protein levels when transfected into prostate cancer cells. At least a dozen distinct types of cancer have the pattern of increased GRN and decreased miR-107 expression. These findings indicate for the first time that the mitogen and growth factor GRN is dysregulated via the miR-15/107 gene group in multiple human cancers, which may provide a potential common therapeutic target. Cancer Res; 70(22); 9137–42. ©2010 AACR.
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Members of the miR-15/107 family have overlapping mRNA targets.
“These miRNAs have overlapping targets.”
From Expression of miR-15/107 Family MicroRNAs in Human Tissues and Cultured Rat Brain Cells (2014) · cites this paper as [11]
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Mendsaikhan, A., Tooyama, I., & Walker, D. G. (2019) · Cells · doi:10.3390/cells8030230 · Cited by 72 · see citing works
Expression of miR-15/107 Family MicroRNAs in Human Tissues and Cultured Rat Brain Cells
Wang, W.-X., Danaher, R. J., Miller, C. S., Berger, J. R., Nubia, V. G., Wilfred, B. S., Neltner, J. H., Norris, C. M., & Nelson, P. T. (2014) · Genomics, Proteomics & Bioinformatics · doi:10.1016/j.gpb.2013.10.003 · Cited by 67 · see citing works
Self-citation
- Authors
- Wang, W.-X., Kyprianou, N., Wang, X., & Nelson, P. T.
- Affiliations
- Authors' Affiliations: 1Department of Pathology and Division of Neuropathology, University of Kentucky Medical Center and Sanders-Brown Center on Aging, University of Kentucky, Lexington, Kentucky and 2Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri
- Venue
- Cancer Research
- Published
- 2010-11-14
- Volume
- 70
- Issue
- 22
- Pages
- 9137-9142
- ISSN
- 0008-5472
- 1538-7445
- PMC
- PMC2982932
- Cited by
- 40
- References
- 0
- Language
- en
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