Polymorphic mature microRNAs from passenger strand of pre-miR-146a contribute to thyroid cancer
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Prior work has shown that heterozygosity G/C of single nucleotide polymorphism (SNP rs2910164) within the precursor of microRNA-146a predisposes to PTC (odds ratio = 1.62, P = 0.000007) although the mechanism was unclear. Here, we show that GC heterozygotes differ from both GG and CC homozygotes by producing 3 mature microRNAs: 1 from the leading strand (miR-146a), and 2 from the passenger strand (miR-146a*G and miR-146a*C), each with its distinct set of target genes. TaqMan analysis of paired tumor/normal samples revealed 1.5- to 2.6-fold overexpression of polymorphic miR-146a* in 7 of 8 tumors compared with the unaffected part of the same gland. The microarray data showed that widely different transcriptomes occurred in the tumors and in unaffected parts of the thyroid from GC and GG patients. The modulated genes are mainly involved in regulation of apoptosis leading to exaggerated DNA-damage response in heterozygotes potentially explaining the predisposition to cancer. We propose that contrary to previously held views transcripts from the passenger strand of miRs can profoundly affect the downstream effects. Heterozygosity for polymorphisms within the premiR sequence can cause epistasis through the production of additional mature miRs. We propose that mature miRs from the passenger strand may regulate many genetic processes.
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A SNP within miR-146a that confers increased risk of thyroid cancer hinders pre-miRNA processing and affects the seed region of the companion miR-146a*.
“Interestingly, one SNP within the miR-146a, which confers an increased risk to develop thyroid cancer, not only hindered the pre-miRNA processing, but also affected the seed region of the companion miR-146a*, similarly to the miR-96(+57T>C) mutation.”
From A novel mutation within the MIR96 gene causes non-syndromic inherited hearing loss in an Italian family by altering pre-miRNA processing (2012) · cites this paper as [26]
miR-146a* is expressed in both normal and tumor thyroid tissues, and altered regulation of miRNA* targets in heterozygotes compared with homozygotes was suggested as a possible mechanism underlying tumor predisposition.
“The miR-146a* was expressed in both normal and tumor thyroid tissues and the altered regulation of the miRNA* targets in heterozygotes compared with homozygotes was suggested as the possible mechanism underlying tumor predisposition (26).”
From A novel mutation within the MIR96 gene causes non-syndromic inherited hearing loss in an Italian family by altering pre-miRNA processing (2012) · cites this paper as [26]
A G/C polymorphism in the miR-146a locus is associated with papillary thyroid carcinoma (PTC) progression.
“In other examples, a G/C polymorphism in the miR‐146a locus, associated with papillary thyroid carcinoma (PTC) progression, alters the sequence of miR‐146a* (3p) strand, and likely leads to changes in target repression, contributing to PTC (Jazdzewski et al., 2009; Labbaye & Testa, 2012), (Table 1).”
From microRNA strand selection: Unwinding the rules (2021) · cites this paper as Jazdzewski et al., 2009
The G/C polymorphism alters the sequence of miR-146a* (3p) strand and likely leads to changes in target repression, contributing to PTC.
“alters the sequence of miR‐146a* (3p) strand, and likely leads to changes in target repression, contributing to PTC (Jazdzewski et al., 2009; Labbaye & Testa, 2012), (Table 1).”
From microRNA strand selection: Unwinding the rules (2021) · cites this paper as Jazdzewski et al., 2009
Cites
DAVID: Database for Annotation, Visualization, and Integrated Discovery
Dennis, G., Sherman, B. T., Hosack, D. A., Yang, J., Gao, W., Lane, H. C., & Lempicki, R. A. (2003) · Genome Biology · doi:10.1186/gb-2003-4-5-p3 · Cited by 9,327 · see citing works
Taganov, K. D., Boldin, M. P., Chang, K.-J., & Baltimore, D. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0605298103 · Cited by 4,317 · see citing works
Exploring genetic interactions and networks with yeast
Boone, C., Bussey, H., & Andrews, B. J. (2007) · Nature Reviews Genetics · doi:10.1038/nrg2085 · Cited by 661 · see citing works
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Regulation of microRNA biogenesis
Ha, M., & Kim, V. N. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3838 · Cited by 5,462 · see citing works
microRNA strand selection: Unwinding the rules
Medley, J. C., Panzade, G., & Zinovyeva, A. Y. (2021) · WIREs RNA · doi:10.1002/wrna.1627 · Cited by 225 · see citing works
Soldà, G., Robusto, M., Primignani, P., Castorina, P., Benzoni, E., Cesarani, A., Ambrosetti, U., Asselta, R., & Duga, S. (2012) · Human Molecular Genetics · doi:10.1093/hmg/ddr493 · Cited by 102 · see citing works
Maussion, G., Yang, J., Yerko, V., Barker, P., Mechawar, N., Ernst, C., & Turecki, G. (2012) · PLoS ONE · doi:10.1371/journal.pone.0039301 · Cited by 91 · see citing works
MicroRNAs as Regulators of Phagocytosis
Gierlikowski, W., & Gierlikowska, B. (2022) · Cells · doi:10.3390/cells11091380 · Cited by 25 · see citing works
- Authors
- Jazdzewski, K., Liyanarachchi, S., Swierniak, M., Pachucki, J., Ringel, M. D., Jarzab, B., & de la Chapelle, A.
- Affiliations
- Human Cancer Genetics Program, Comprehensive Cancer Center and
- Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, 44-101 Gliwice, Poland; and
- Medical University of Warsaw (PL)
- The Ohio State University (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2009-02-03
- Volume
- 106
- Issue
- 5
- Pages
- 1502-1505
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2635764
- OpenAlex
- W1980735015
- Cited by
- 304
- References
- 3
- Citations by year
- 2025: 1 · 2024: 6 · 2023: 4 · 2022: 9 · 2021: 7 · 2020: 11 · 2019: 12 · 2018: 14 · 2017: 14 · 2016: 16 · 2015: 24 · 2014: 36 · 2013: 38 · 2012: 33
- FWCI
- 12.53
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ohio State University (CA16058)
- National Cancer Institute (CA124570, CA16058, P01CA124570, P30CA016058)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Keywords
- microRNA-146a, miR-146a, thyroid cancer, papillary thyroid carcinoma, genetic susceptibility, heterozygosity, epistasis, apoptosis regulation, DNA damage response, miRNA target genes, transcriptome
- MeSH terms
- Base Sequence, Heterozygote, Humans, RNA Precursors, RNA, Messenger, Thyroid Neoplasms, Apoptosis, DNA Primers, Reverse Transcriptase Polymerase Chain Reaction, Polymorphism, Single Nucleotide, MicroRNAs, Cell Line, Tumor
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