Abstract
Single nucleotide polymorphisms (SNPs) in miRNA biosynthesis genes DROSHA and DGCR8 were indicated to be correlated with cancer risk. We comprehensively reviewed and analyzed the effect of DROSHA and DGCR8 polymorphisms on cancer risk. Eligible articles were selected according to a series of inclusion and exclusion criteria. Consequently, ten case–control studies (from nine citations) with 4265 cancer cases and 4349 controls were involved in a meta-analysis of seven most prevalent SNPs (rs10719 T/C, rs6877842 G/C, rs2291109 A/T, rs642321 C/T, rs3757 G/A, rs417309 G/A, rs1640299 T/G). Our findings demonstrated that the rs417309 SNP in DGCR8 was significantly associated with an elevated risk of overall cancer in every genetic model. In stratified analysis, correlations of DROSHA rs10719 and rs6877842 SNPs were observed in Asian and laryngeal cancer subgroups, respectively. Moreover, associations of the rs417309 SNP could also be found in numerous subgroups including: Asian and Caucasian population subgroups; laryngeal and breast cancer subgroups; population-based (PB) and hospital-based (HB) subgroups. In conclusion, the DROSHA rs10719, rs6877842 SNPs, and DGCR8 rs417309 SNP play pivotal roles in cancerogenesis and may be potential biomarkers for cancer-forewarning.
Highlights
MiRNAs are a type of small non-coding RNAs that play roles at post-transcriptional level by sequence-specific binding to the 3 -UTRs of target mRNAs [1]
For rs10719 T/C single nucleotide polymorphism (SNP), its homozygote variant genotype and recessive models were correlated with an elevated cancer risk in Asian (CC compared with TT: odds ratio (OR) = 1.230, 95% 95% confidence interval (CI) = 1.001–1.511, P=0.048; cervical cancer (CC) + CT compared with TT: OR = 1.223, 95% confidence intervals (95% CIs) = 1.002–1.494, P=0.048, Table 3)
For rs6877842 G/C SNP, its heterozygote model had strong correlation with a reduced risk of laryngeal cancer (CG compared with GG: OR = 0.413, 95% CI = 0.193–0.881, P=0.022, Table 3) and its homozygote variant genotype, dominant and allelic models had moderate associations with a descending risk of laryngeal cancer (CC compared with GG: OR = 0.604, 95% CI = 0.417–0.875, P=0.008; CC compared with CG + GG: OR = 0.573, 95% CI = 0.401–0.819, P=0.002; C compared with G: OR = 0.638, 95% CI = 0.481–0.847, P=0.002, Table 3)
Summary
MiRNAs are a type of small non-coding RNAs that play roles at post-transcriptional level by sequence-specific binding to the 3 -UTRs of target mRNAs [1]. During the miRNA maturing processing, primary miRNAs (pri-miRNAs) are first synthesized by RNA II polymerase in nucleus. They are converted into precursor miRNAs (pre-miRNAs) by a Drosha–DGCR8 microprocessor complex which is constituted by DROSHA, an RNase III superfamily member and its cofactor DGCR8 [2]. Far, accumulating studies have been concerned with the association between DROSHA and DGCR8 c 2018 The Author(s).
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