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Single nucleotide polymorphisms at miR-146a/196a2 and their primary ovarian insufficiency-related target gene regulation in granulosa cells.

ABSTRACT: MicroRNAs post-transcriptionally regulate gene expression in animals and plants. The aim of this study was to identify new target genes for microRNA polymorphisms (miR-146aC>G and miR-196a2T>C) in primary ovarian insufficiency (POI). We cloned and transfected miR-146aC>G and miR-196a2T>C into human granulosa cells and used microarrays and qPCR-arrays to examine the changes in the messenger RNA expression profile. We show miR-146aC>G and miR-196a2T>C change the mRNA expression patterns in granulosa cell. In each case, mRNAs were up or down-regulated after treatments with miR-146a C or G and miR-196a2 T or C. We found that miR-146a led to a significantly altered regulation of the mRNA levels of FOXO3, FOXL2 and CCND2 compared to controls. We also found that the polymorphisms of miR-146a led to a significantly altered regulation of CCND2 and FOXO3. Our results suggest that miR-146aC>G and miR-196a2T>C can regulate the levels of many of their target transcripts. In addition, specific target genes of miR-146aC>G polymorphisms may be involved in granulosa cell regulation.

SUBMITTER: Cho SH

PROVIDER: S-EPMC5571913 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Single nucleotide polymorphisms at miR-146a/196a2 and their primary ovarian insufficiency-related target gene regulation in granulosa cells.

Cho Sung Hwan SH An Hui Jeong HJ Kim Kyung Ah KA Ko Jung Jae JJ Kim Ji Hyang JH Kim Young Ran YR Ahn Eun Hee EH Rah HyungChul H Lee Woo Sik WS Kim Nam Keun NK

PloS one 20170825 8

MicroRNAs post-transcriptionally regulate gene expression in animals and plants. The aim of this study was to identify new target genes for microRNA polymorphisms (miR-146aC>G and miR-196a2T>C) in primary ovarian insufficiency (POI). We cloned and transfected miR-146aC>G and miR-196a2T>C into human granulosa cells and used microarrays and qPCR-arrays to examine the changes in the messenger RNA expression profile. We show miR-146aC>G and miR-196a2T>C change the mRNA expression patterns in granulo ...[more]

PMID: 28841705

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Project description:Background: Cervical cancer is the second major female cancer in India and constitutes one-fourth of the world's burden. Human Papilloma Virus (HPV) infection is an essential but insufficient cause for cervical cancer. Genetic variants in microRNAs (miRNAs/miRs) play an important role in the susceptibility of various types of cancers.Objective: To evaluate the association of Single Nucleotide Polymorphisms (SNPs) in miR-146a (rs2910164), miR-196a2 (rs11614913), and miR-499 (rs3746444), with cervical cancer susceptibility in Indian population.Methods: Three hundred samples were genotyped by Polymerase chain reaction (PCR)-Restriction fragment length polymorphism (RFLP). Both patients and controls were also screened for the presence of HPV DNA.Results: In this case-control study, 125 (83.3%) cervical cancer cases were found to be infected with HPV DNA. The frequency of miR-146a C allele was higher in controls than in cases [odds ratio (OR) (95% confidence interval (CI)) = 0.81 (0.57-1.14), P-value = 0.258]. miR-196a2 T allele was found to be associated with the decreased risk of cervical cancer [OR (95% CI) = 0.36 (0.26-0.50), P-value<0.0001]. Approximately 1.22-fold increased risk has been observed in individuals carrying miR-499 TT genotypes [OR (95% CI) = 1.22 (0.63-2.36), P-value = 0.617]. Interaction studies for miR-196a2/miR-499 loci showed that women carrying TT/CC and TT/CT genotypes were less likely to develop cervical cancer than CC/CC combination [P<0.05]. Likewise, miR-146a/miR-196a2 genotypic combinations (CC/TT, CG/TT, GG/TT) followed the similar trend [P<0.05], exhibited the protective effect against cervical cancer with reference to CC/CC group. Combined genotypes of miR-146a/miR-499 [CC/CT, CG/CC, CG/CT, CG/TT, GG/CC, GG/CT, GG/TT] demonstrated a non-significant trend toward higher cervical cancer risk [OR > 1.00, P>0.05].Conclusion: Polymorphisms in miR-146a, miR-196a2, and miR-499 individually or collectively have the prospective to emerge as biomarkers for cervical cancer.

Project description:BackgroundMicroRNAs regulate gene expression at the post-transcriptional level and involved in diverse biological and pathological processes, including tumorigenesis. Rs11614913 in miR-196a2 and rs2910164 in miR-146a are shown to associate with increased/decreased cancer risk. We performed a meta-analysis to systematically summarize the possible association.Methodology/principal findingsWe assessed published studies of the association between these microRNA polymorphisms and cancer risk from eleven studies with 16,771 subjects for miR-196a2 and from ten studies with 15,126 subjects for miR-146a. As for rs11614913, the contrast of homozygote (TT vs CC: OR = 0.92, 95% CI = 0.85-0.99, P(heterogeneity) = 0.45), allele (T vs C: OR = 0.96, 95% CI = 0.92-0.99, P(heterogeneity) = 0.61) and recessive model (OR = 0.90, 95% CI = 0.84-0.97, P(heterogeneity) = 0.50) produced statistically association. Subgroup analysis by ethnicity, statistically significantly decreased cancer risks were found among Asians for allele contrast (OR = 0.95, 95% CI = 0.90-0.99, P(heterogeneity) = 0.74) and the recessive genetic model (OR = 0.90, 95% CI = 0.82-0.98, P(heterogeneity) = 0.85). According to subgroup analysis by tumor types, the protective effect of C/T polymorphism was only found in breast cancer under allele contrast (T vs C: OR = 0.94, 95% CI = 0.88-0.99, P(heterogeneity) = 0.26). For rs2910164, no significant associations were found among overall analysis model with relatively large heterogeneity. Through the stratified analysis, heterogeneity decreased significantly. In the subgroup analyses by cancer types, the C allele of rs2910164 was associated with protection from digestive cancer in allele contrast (C vs G: OR = 0.86, 95% CI = 0.77-0.96, P(heterogeneity) = 0.51).Conclusions/significanceOur meta-analysis suggests that the rs11614913 most likely contributes to decreased susceptibility to cancer, especially in Asians and breast cancer. Besides, the C allele of the rs2910164 might be associated with a protection from digestive cancer.

Dataset Information

Single nucleotide polymorphisms at miR-146a/196a2 and their primary ovarian insufficiency-related target gene regulation in granulosa cells.

Publications

Single nucleotide polymorphisms at miR-146a/196a2 and their primary ovarian insufficiency-related target gene regulation in granulosa cells.

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