Abstract
The current study aimed to investigate how the rs12402181 variant in the miR-3117-3p seed region affects miRNA processing and binding ability to the target sequences and breast cancer susceptibility. To study the role of rs12402181 polymorphism in breast cancer, blood samples were examined to investigate the possible association between the genetic variant in the miR-3117 and breast cancer susceptibility. The miR-3117 gene variant was genotyped using PCR–RFLP. The pre-miR-3117 and parts of the flanking region with GG or AA genotype were inserted into a pEGFPN1 expression vector and followed by qPCR to evaluate the effect of SNP on miR-3117-3p expression levels and function. Cell proliferation and migration properties investigated by MTT and wound healing assay. Web server databases were used for further investigation of potential changes in miRNA function. Genotype frequency study in breast cancer patients and healthy controls showed that rs12402181 polymorphism (G > A) is inversely associated with susceptibility to breast cancer (P = 0.03, OR 0.551). The variant allele led to increased production of mature miR-3117 and reduced cell proliferation and migration in MCF7 and T47D cells. These findings suggest that A allele in miR-3117-3p affects the processing of miRNA, causing an increase in the miRNA mature form which can negatively regulate tumor development and migration.
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The data analyzed during the present study are available from the corresponding author upon reasonable request.
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The authors are responsible for all aspects of the study in ensuring that questions related to the accurateness or reliability of any part of the work are appropriately investigated and resolved. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. The samples with research ethics code IR.SKU.REC.1399.005 has been approved by research ethics committee at Shahrekord University, Iran. As well as, informed consent was obtained from all individual participants included in the study.
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Mirabbasi, R., Ebrahimi, S.O., Tavakoli, F. et al. Novel polymorphism rs12402181 in the mature sequence of hsa-miR-3117-3p has a protective effect against breast cancer development by affecting miRNA processing and function. 3 Biotech 13, 349 (2023). https://doi.org/10.1007/s13205-023-03765-y
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DOI: https://doi.org/10.1007/s13205-023-03765-y