Association study of SNPs in LncRNA CDKN2B-AS1 with breast cancer susceptibility in Chinese Han population. (February 2022)

• Record Type: Journal Article
• Authors: Sun, Qiuyu; Chong, Feifei; Jiang, Xiaoru; Wang, Yanli; Xu, Kedi; Zou, Yuanlin; Song, Chunhua
• Is Part Of: International journal of biochemistry & cell biology. Volume 143(2022)
• Publication Date: 2022-02
• Subjects: SNPs Single Nucleotide Polymorphisms -- MDR multifactor dimentsionality reduction -- qRT–PCR Quantitative real-time PCR -- ER estrogen receptor -- PR progesterone receptor -- HER-2 human epidermal growth factor receptor-2 -- MAF minor allele frequency -- FPRP False positive report probability; Breast cancer -- CDKN2B-AS1 -- SNPs -- Genetic susceptibility -- Function; Biochemistry -- Periodicals; Cytology -- Periodicals; Biochemistry -- Periodicals; Cell Biology -- Periodicals; Biochimie -- Périodiques; Cytologie -- Périodiques; Biochimie; Cytologie; Biochemistry; Cytology; Ressource Internet (Descripteur de forme); Périodique électronique (Descripteur de forme); Periodicals; 572.05
• DOI: 10.1016/j.biocel.2021.106139
• Languages: English
• ISSNs: 1357-2725

Abstract

Abstract: Background: The study aimed to analysis the genetic variation of the lncRNA CDKN2B-AS1 SNPs, and explored the regulation of SNPs on the invasion and metastasis of Breast cancer (BC). Methods: The SNPs (Single Nucleotide Polymorphisms) was screened for genotyping among 504 Chinese Han patients and 505 controls, which were frequency-matched for age ( ± 2 years). Logistic analysis was to explore the relationship between SNPs and the BC risk. Interactions between SNPs and reproductive factors was explored using the multifactor dimensionality reduction (MDR) method. qRT–PCR was conducted to detect the CDKN2B-AS1 expression in plasma of different rs10965215 and rs2518723 genotypes. The effect of rs10965215 A>G mutation on the binding ability of CDKN2B-AS1 and miR-4440 was verified by dual luciferase experiment. CCK-8, scratch and Transwell experiment were performed to explore the effect of miR-4440 over-expression on BC cell proliferation, migration and invasion. Results: A total of 13 SNP was screened. The individuals with SNPs rs2518723C>T, rs10965215 A>G, rs77792598C>G, rs4977753 T > C, rs75917766C>T and rs78545330C>G mutations might increase the BC risk. MDR results revealed that individuals with rs10965215 G genotype who age at menarche≥ 13 and regardless of the number of abortion< 2 or ≥ 2 had a higher risk of BC. The relative expression of CDKN2B-AS1 in rs10965215 homozygous wild AA genotype (8.88 ± 3.43) was lower than heterozygous GA (11.08 ± 2.90) and homozygous mutant GG genotype (11.31 ± 2.90). When rs10965215 wild A genotype was carried, there was an interaction between CDKN2B-AS1 and miR-4440. The CCK-8, Transwell, and scratch experiment were all found that miR-4440 over-expression might enhance the proliferation, invasion and migration of BC cells. - Conclusion: CDKN2B-AS1 gene polymorphism might be related to the susceptibility of BC, CDKN2B-AS1 rs10965215 A/G genotype probably affect the proliferation, invasion and migration of BC cells by modulating the interactions with of miR-4440. Highlights: Individuals with CDKN2B-AS1 SNPs rs10965215 G>A mutation may increase the risk of BC. The individuals with rs10965215 G genotype, age at menarche≥ 13 and had history increase the risk of BC. The CDKN2B-AS1 expression in plasma of rs10965215 AA genotype was lower than GA and mutant GG. There was an interaction between CDKN2B-AS1 and miR-4440 when carried rs10965215 wild A genotype. CDKN2B-AS1 rs10965215 A>G mutation may mediate the interaction between CDKN2B-AS1 and miR-4440, and then improve the proliferation, invasion and migration of BC cells.