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Characterization of lncRNA LINC00520 and functional polymorphisms associated with breast cancer susceptibility in Chinese Han population.

ABSTRACT: BACKGROUND:The aim was to evaluate the association between the LINC00520 genetic polymorphisms and breast cancer (BC) susceptibility. METHODS:Nine single-nucleotide polymorphisms (SNPs) on LINC00520 genotyping were performed in 504 BC patients and 505 cancer-free controls in Chinese Han population to study the relationship between LINC00520 polymorphism and BC susceptibility. qRT-PCR and luciferase tests were used to explore how rs12880540 affected the expression of LINC00520. RESULTS:The genotype GG (OR:3.58, 95%CI:1.32-9.69) in rs8012083 increased the risk of triple-negative BC. The genotype GG (OR:0.31, 95%CI:0.14-0.69) in rs8012083, the genotype AA (OR:2.74, 95%CI:1.01-7.42) in rs2152275, and genotype TG (OR:1.62, 95%CI:1.04-2.52) in rs12880540 were associated with HER-2 status. The dominant (OR:0.65, 95%CI:0.45-0.95) and overdominant genetic model (OR:0.67, 95%CI:0.46-0.98) consistently showed that rs11622641 T was significantly associated with lower risk of BC. Similarly, the recessive genetic model (OR:1.57, 95%CI:1.07-2.30) of rs12880540 and the dominant (OR:1.62, 95%CI:1.24-2.11) and overdominant (OR:1.56, 95%CI:1.19-2.03) genetic model of rs2152278 may increase the risk of BC. The relative expression of LINC00520 increased linearly with the increase in the number of rs12880540 mutations. rs12880540 alleles were due to the interaction between LINC00520 and miR-3122 at T, but the mutation of rs12880540 G > T had no effect on the binding ability of LINC00520 and miR-3122. CONCLUSION:A genetic variant of rs8012083 in LINC00520 may be used as a biomarker for triple-negative BC after further evaluation of diagnostic tests. The genetic variant of LINC00520 was related to the susceptibility of BC, and rs12880540 might affect the corresponding mRNA expression of lncRNA LINC00520.

SUBMITTER: Guo Q

PROVIDER: S-EPMC7064040 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Characterization of lncRNA LINC00520 and functional polymorphisms associated with breast cancer susceptibility in Chinese Han population.

Guo Qiaoyun Q Xu Linping L Peng Rui R Ma Yan Y Wang Yanli Y Chong Feifei F Song Mengmeng M Dai Liping L Song Chunhua C

Cancer medicine 20200129 6

<h4>Background</h4>The aim was to evaluate the association between the LINC00520 genetic polymorphisms and breast cancer (BC) susceptibility.<h4>Methods</h4>Nine single-nucleotide polymorphisms (SNPs) on LINC00520 genotyping were performed in 504 BC patients and 505 cancer-free controls in Chinese Han population to study the relationship between LINC00520 polymorphism and BC susceptibility. qRT-PCR and luciferase tests were used to explore how rs12880540 affected the expression of LINC00520.<h4> ...[more]

PMID: 31997582

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Project description:BackgroundPublished studies based on pharmacokinetics have explored the relationship between the lncRNA MIR2052HG and the prognosis of breast cancer (BC) resistance and recurrence. However, the underlying association of MIR2052HG SNPs with BC development remains unclear.MethodsCombining bioinformatics and databases, SNPs (Single Nucleotide Polymorphisms) in the MIR2052HG gene were screened, and SNPs in the lncRNA MIR2052HG were selected for genotyping among 504 Chinese Han patients and 505 healthy controls, which were frequency-matched for age (±2 years). Logistic regression analysis was used to explore the association between MIR2052HG SNPs and the BC risk. Interactions between the MIR2052HG SNPs and reproductive factors were further evaluated using the multifactor dimensionality reduction (MDR) method. qRT-PCR was performed to detect MIR2052HG expression in individuals with different genotypes of rs34841297. The target miRNA, miR-4456 of MIR2052HG rs34841297 was predicted by websites and confirmed by performing dual luciferase gene reporter assays. CCK-8 and Transwell experiments were designed to explore the effects of miR-4456 on the proliferation, invasion and migration of BC cells.ResultsIn this study, nine SNPs were screened. After adjusting for age, menarche age, menopausal status, number of pregnancies, history of abortions, breast feeding history and family history of BC, the results of the logistic regression analysis showed the rs34841297 A/- gene polymorphism was positively correlated with the incidence of BC. Compared with the AA genotype, patients with the A-+-- genotype of rs34841297 at age<50 years, and menarche age<14 years, Premenopausal status, history of abortion, no history of breastfeeding and no family history of tumors in first-degree relatives had an increased risk of BC. MDR results revealed that individuals with rs34841297 - (homozygous deletion) of the A allele who were not menopausal and had no history of breastfeeding had a higher risk of BC. qRT-PCR results revealed that homozygous deletion (1.68±1.37) of the rs34841297 A- genotype resulted in higher MIR2052HG expression than the heterozygous deletion genotype (0.95±0.94) and wild AA genotype (0.26±0.12). Binding between MIR2052HG and miR-4456 was occurred when rs34841297 carried the AA genotype. Moreover, preliminary functional studies indicated that the overexpression of miR-4456 increased the proliferation, invasion and migration of BC cells.ConclusionOur study showed that the MIR2052HG gene polymorphism may be related to BC susceptibility, and the MIR2052HG rs34841297 A/- genotype may probably affect the proliferation, invasion and migration of BC cells by modulating the interactions with of miR-4456.

Dataset Information

Characterization of lncRNA LINC00520 and functional polymorphisms associated with breast cancer susceptibility in Chinese Han population.

Publications

Characterization of lncRNA LINC00520 and functional polymorphisms associated with breast cancer susceptibility in Chinese Han population.

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