A functional polymorphism rs4938723 in the promoter of miR-34b/c is associated with an increased risk of lung cancer


Çelik A., Karakaş Çelik S., Arpacı E., Engin H., Arıcan E.

JOURNAL OF EXPERIMENTAL AND MOLECULAR BIOLOGY, vol.25, no.1, pp.1-11, 2023 (SCI-Expanded)

Abstract

Background:The expression levels of some microRNAs (miRNAs) in lung cancer have been associated with an increased risk of cancer. miRNAs play a significant role in the pathogenesis of   human   cancers.   Because   of   this,   miRNA   polymorphisms   can   be   important   for carcinogenesis. MiR-34 is a family of miRNAs known to have reduced levels of expression in lung cancer and other human cancers (pancreas, colon). It functions as a tumor suppressor and targets oncogenes such as MET, RET, and RAB43. Additionally, the miR-125 family is related to many cancer types and targets P53, BCL2, VEGF, and EGFR.Methods:In this study, we investigated three polymorphisms (rs35301225 C/A, T, rs4938723 T/C,  and  rs12976445  C/T)  in  respectively  miR-34a,  miR-34b/c,  and  miR-125a.  The  study population consisted of 100 patients with lung cancer and 100 healthy controls. Blood samples was  collected  into  EDTA-containing  tubes  and  genomic  DNA  was  extracted.  Genetic polymorphisms were identified using the polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP). Results:We observed that individuals carrying the miR-34b/c rs4938723 variant heterozygote CT exhibited a significant increase in the risk of lung cancer when compared to those with the wild-type   homozygote   TT   (p<0.01). Moreover,   the   presence   of   the   C   allele   in   this polymorphism  was  significantly  associated  with  an  elevatede  risk  of  lung  cancer  (p<0.001). Additionally,  the  T/T  haplotype  of  miR-34b/c  and  miR125a  polymorphisms  was found  to confer a protective effect against lung cancer in ourhaplotype analysis (p<0.001).Conclusions:The rs4938723 polymorphism in miR-34b/c is thought to play an essential role in the pathogenesis of lung cancer. The frequency of the T/T haplotype for rs4938723/rs12976445 polymorphisms  was  significantly  higher  in  the  control  group  compared  to  the  group of  lung cancer patients.

 

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