Journal article
miR-17 acts as a tumor suppressor by negatively regulating the miR-17-92 cluster
Molecular therapy. Nucleic acids, Vol.26, pp.1148-1158
12/03/2021
DOI: 10.1016/j.omtn.2021.10.021
PMCID: PMC8601969
PMID: 34853714
Abstract
Anaplastic thyroid cancer (ATC) is an aggressive, highly metastatic cancer that expresses high levels of the microRNA (miR)-17-92 cluster. We employ an miR inhibitor system to study the function of the different miRs within the miR-17-92 cluster based on seed sequence homology in the ATC SW579 cell line. While three of the four miR-17-92 families were oncogenic, we uncovered a novel role for miR-17 as a tumor suppressor in vitro and in vivo. Surprisingly, miR-17 inhibition increased expression of the miR-17-92 cluster and significantly increased the levels of the miR-18a and miR-19a mature miRs. miR-17 inhibition increased expression of the cell cycle activator CCND2, associated with increased cell proliferation and tumor growth in transplanted SW579 cells in xenograft mice. miR-17 regulates MYCN and c-MYC expression in SW579 cells, and the inhibition of miR-17 increased MYCN and c-MYC expression, which increased pri-miR-17-92 transcripts. Thus, inhibition of miR-17 activated the expression of the oncogenic miRs, miR-18a and miR-19a. While many cancers express high levels of miR-17, linking it with tumorigenesis, we demonstrate that miR-17 inhibition does not inhibit thyroid tumor growth in SW579 and MDA-T32 ATC cells but increases expression of the other miR-17-92 family members and genes to induce cancer progression.
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Cancer cells and tumors have characteristic microRNA (miR) profiles and high-expressing miRs are linked to poor survival rates in patients and maybe therapeutic targets. In contrast, inhibiting miR-17 in anaplastic thyroid cancer (ATC) results in significantly increased tumor formation due to activation of the miR-17-92 cluster and tumor-inducing genes.
Details
- Title: Subtitle
- miR-17 acts as a tumor suppressor by negatively regulating the miR-17-92 cluster
- Creators
- Yan Sweat - Harvard UniversityRyan J. Ries - Cornell UniversityMason Sweat - Harvard UniversityDan Su - University of IowaFan Shao - University of IowaSteven Eliason - University of IowaBrad A. Amendt - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Molecular therapy. Nucleic acids, Vol.26, pp.1148-1158
- DOI
- 10.1016/j.omtn.2021.10.021
- PMID
- 34853714
- PMCID
- PMC8601969
- NLM abbreviation
- Mol Ther Nucleic Acids
- ISSN
- 2162-2531
- eISSN
- 2162-2531
- Publisher
- Elsevier Inc
- Grant note
- DOI: 10.13039/100000002, name: National Institutes of Health, award: 5T90DE023520, DE028527
- Language
- English
- Date published
- 12/03/2021
- Academic Unit
- Orthodontics; Anatomy and Cell Biology; Craniofacial Anomalies Research Center; Dental Research
- Record Identifier
- 9984284351002771
Metrics
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