Potentially functional variants in lncRNAs are associated with breast cancer risk in a Chinese population

Abstract

Long non-coding RNAs (lncRNAs) participate in the development of breast cancer. Genetic variants in lncRNAs may be involved in their abnormal expressions and associated with cancer risk. In the present study, we performed RNA sequencing on five paired breast cancer tumor and adjacent non-cancerous tissues to obtain differentially expressed lncRNAs. We systematically selected potential regulatory variants of these lncRNAs and investigated the associations between these variants and breast cancer susceptibility in 1486 breast cancer cases and 1519 cancer-free controls in a Chinese population. Eleven lncRNAs were significantly differentially expressed between breast cancer tumor and normal tissues (false discovery rate (FDR) ≤0.05 and fold-change ≥2), including two known lncRNAs HOTAIR and UCA1. We subsequently genotyped 20 variants located on these lncRNAs and identified two variants (rs11471161 in AC104135.3 and rs3751232 in RP11-1060J15.4) associated with breast cancer risk. Logistic regression analysis indicated that the variant allele of rs11471161 was significantly associated with a decreased breast cancer risk (additive model: OR = 0.84, 95%CI = 0.74-0.94, P = 0.004), while the variant allele of rs3751232 showed an increased risk of breast cancer (additive model: OR = 1.20, 95%CI = 1.02-1.40, P = 0.027). Further co-expression analysis indicated that AC104135.3 associated with ERBB2, which promotes the development and progression of breast cancer through overexpression. Together, these results suggest that genetic variants rs11471161 and rs3751232 in AC104135.3, and RP11-1060J15.4, respectively, may influence the susceptibility to breast cancer in the Chinese population. Further functional evaluations and larger studies are warranted to validate these findings.

Long Non-Coding RNA in the Pathogenesis of Cancers

“…Further study has suggested that the plasma HOTAIR level is positively associated with lymph node metastasis and estrogen receptor, and reduced after surgery in BC patients [118]. Genetic polymorphisms of HOTAIR are associated with BC risk in different races [119,120,121]. The latest findings suggest that HOTAIR-containing exosomes could be detected in BC patients’ blood [122,123].…”

The long noncoding RNA TINCR promotes breast cancer cell proliferation and migration by regulating OAS1

“…Although the treatment of breast cancer has made great progress and the mortality rate has decreased year by year, due to the high incidence of tumor specific death, the prognosis of patients is still worthy of attention 2,3 . There are about 1.7 million new cases every year in the world, accounting for 25% of all new cancer cases among women 4 . According to the data from the Centers for Disease Control and Prevention (CDC) 5 , 245,299 new breast cancer cases occurred in the United States in 2016, and 41,487 women died of breast cancer.…”

Downregulation of LINC01140 is associated with adverse features of breast cancer

“…Therefore, understanding the regulatory network underlying BC is an essential focus point for future studies. There is an increasing amount of evidence that long non-coding RNAs (lncRNAs) participate in the development and progression of BC and potentially serve as markers of diagnosis or prognosis (4,5).…”