Dataset Information

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.

SUBMITTER: Lai GE

PROVIDER: S-EPMC9177277 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Publications

A combination of transcriptome and methylation analyses reveals the role of lncRNA <i>HOTAIRM1</i> in the proliferation and metastasis of breast cancer.

Lai Gui-E GE Zhou Jian J Huang Cui-Liu CL Mai Cun-Jun CJ Lai Yi-Mei YM Lin Zhi-Qin ZQ Peng Tao T Luo Yuan Y Liu Feng-En FE

Gland surgery 20220501 5

<h4>Background</h4>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.<h4>Methods</h4>We retrieved transcriptome and DNA methylation profiles of BRCA patients from The Cancer Genome Atlas (TCGA) database, then applied the "limma" package in R sof ...[more]

PMID: 35694102

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