A combination of transcriptome and methylation analyses reveals the role of lncRNA HOTAIRM1 in the proliferation and metastasis of breast cancer

Abstract

Background: DNA methylation status is strongly associated with the prognosis of breast invasive carcinoma (BRCA). Elucidating the mechanisms underlying DNA methylation coupled with determining its biological function is imperative to the effective development of treatment and prevention strategies for breast cancer.Methods: We retrieved transcriptome and DNA methylation profiles of BRCA patients from The Cancer Genome Atlas (TCGA) database, then applied the "limma" package in R software to identify differentially expressed genes (DEGs) and aberrantly methylated genes. Next, we used the "MethylMix" package to screen for methylation-driven genes, and performed univariate and multivariate Cox regression analyses to determine the prognostic value of the methylation-driven genes and clinical characteristics. We validated these findings in 51 breast cancer tissues alongside 51 corresponding normal tissues. Furthermore, we used cell experiments to clarify the biological function and underlying molecular mechanisms of HOTAIRM1 in vitro.Results: A total of 25 methylation-driven genes were identified in the dataset. Results from univariate and multivariate Cox regression showed that SYN2, HOTAIRM1, BCAS1, and ALDOC were significantly associated with patient prognosis. Immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR) results showed that the expression levels of SYN2 and HOTAIRM1 were negatively correlated with BRCA stage, whereas those of BCAS1 and ALDOC were positively correlated with BRCA stage. Results from in vitro experiments showed that knockdown HOTAIRM1 expression promoted breast cancer cells proliferation, clone formation, and invasion. Up-regulation of HOTAIRM1 inhibited breast cancer cells proliferation, clone formation, and invasion.Conclusions: In summary, low HOTAIRM1 expression is a significant prognostic factor for the survival of BRCA patients and thus could be a potential therapeutic target for the treatment of BRCA.

Experimental Identification of Aberrantly Expressed Long Non-Coding RNAs in Breast Cancer

“…The lncRNA HOTAIRM1 has already been proposed as a biomarker for oral squamous cell carcinoma [28], and its role in the proliferation and metastasis of breast cancer has also been proposed [29]; the development of resistance to tamoxifen therapy due to the regulation of HOXA1 protein expression is being studied [30].…”