Association study of SNPs in LncRNA CDKN2B-AS1 with breast cancer susceptibility in Chinese Han population

Qiuyu Sun; Feifei Chong; Xiaoru Jiang; Yanli Wang; Kedi Xu; Yuanlin Zou; Chunhua Song

doi:10.1016/j.biocel.2021.106139

Association study of SNPs in LncRNA CDKN2B-AS1 with breast cancer susceptibility in Chinese Han population

Int J Biochem Cell Biol. 2022 Feb:143:106139. doi: 10.1016/j.biocel.2021.106139. Epub 2021 Dec 22.

Authors

Qiuyu Sun¹, Feifei Chong¹, Xiaoru Jiang¹, Yanli Wang¹, Kedi Xu¹, Yuanlin Zou¹, Chunhua Song²

Affiliations

¹ Department of Epidemiology and Statistics, College of Public Health, Zhengzhou University, 100 Science Avenue, Zhengzhou 450001, Henan Province, China; Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, 40 Daxue Road, Zhengzhou 450052, Henan Province, China; State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan Province 450052, China.
² Department of Epidemiology and Statistics, College of Public Health, Zhengzhou University, 100 Science Avenue, Zhengzhou 450001, Henan Province, China; Henan Key Laboratory of Tumor Epidemiology, Zhengzhou University, 40 Daxue Road, Zhengzhou 450052, Henan Province, China; State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan Province 450052, China. Electronic address: sch16@zzu.edu.cn.

PMID: 34954153
DOI: 10.1016/j.biocel.2021.106139

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.

Keywords: Breast cancer; CDKN2B-AS1; Function; Genetic susceptibility; SNPs.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Breast Neoplasms / genetics*
Breast Neoplasms / pathology
Case-Control Studies
China
Female
Genotype
Humans
Middle Aged
Polymorphism, Single Nucleotide / genetics*
RNA, Long Noncoding / genetics

Substances

RNA, Long Noncoding