Concise approach for screening long non-coding RNAs functionally linked to human breast cancer associated genes

Abstract

Cancer research studies using next-generation sequencing have revealed a number of genes of which aberrant expression is associated with various cancers. Recently, long non-coding RNA (lncRNA) has been highlighted due to its tissue-specific expression and cell cancerization functions, such as the regulation of key tumor suppressors. In this study, we suggest a very efficient approach to survey lncRNAs putatively associated with breast cancer. We targeted lncRNAs linked with breast cancer associated genes (BCAGs) and analyzed their expression pattern in human breast cancer cell lines. A total of 337 BCAGs were retrieved from literature review and the existence of 121 lncRNAs were identified from the 15 kb up- and downstream regions of the list of genes. Twenty lncRNAs' expression were detectable in human breast cancer cell lines with different expression patterns. Interestingly, the expression of three lncRNAs, two up-regulated (RAD51C v.4, LOC105371849) and one down-regulated (LOC102724064), were closely correlated with adjacent BCAGs (RAD51C, HEATR6 and BRMS1) in breast cancer cell lines. We thus demonstrated association between the lncRNA and its adjacent BCAG using LOC105371849-HEATR6, of which the function and regulation in breast cancer are still unknown. Knockdown of LOC105371849 by siRNA decreased the expression of HEATR6 mRNA in the MCF7 human breast cancer cell line. In conclusion, this study provides a better understanding about the biological roles of lncRNAs in breast cancer and may be useful in the investigation of proper targets for diagnostic and/or therapeutic breast cancer markers using public databases.

Keywords: Antisense RNA; Breast cancer; Breast cancer associated genes; Cis-regulation; Comparative medicine; LncRNA; Long non-coding RNA.