Upregulation of LINC00511 expression by DNA hypomethylation promotes the progression of breast cancer

Chunxiao Liu; Yuting Xu; Xu Liu; Yingqiang Fu; Kaiyuan Zhu; Zhenbo Niu; Jiaxin Liu; Cheng Qian

doi:10.21037/gs-21-84

Upregulation of LINC00511 expression by DNA hypomethylation promotes the progression of breast cancer

Gland Surg. 2021 Apr;10(4):1418-1430. doi: 10.21037/gs-21-84.

Authors

Chunxiao Liu¹, Yuting Xu¹, Xu Liu¹, Yingqiang Fu¹, Kaiyuan Zhu¹, Zhenbo Niu¹, Jiaxin Liu¹, Cheng Qian^{1

2}

Affiliations

¹ Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, China.
² Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, China.

Abstract

Background: LINC00511 is a newly discovered long intergenic nonprotein-coding RNA (Ribonucleic acid) with unknown.

Method: Differential gene expression analysis was performed on breast cancer microarray data, and the upregulated expression of LINC00511 in breast cancer tissues and breast cancer cell lines was verified by qRT-PCR (quantitative Reverse Transcription-Polymerase Chain Reaction). A cohort study revealed a correlation between the expression of LINC00511 and the clinicopathological features in breast cancer patients. The effects of LINC00511 on breast cancer migration and invasion were studied in vitro. Then, an experiment using the Illumina Infinium Human Methylation450 Beadchip data was conducted to study the role of DNA (Deoxyribonucleic acid) methylation in LINC00511 expression, and DAVID (Database for Annotation, Visualization and Integrated Discovery) Functional Annotation Bioinformatics Microarray Analysis was used to determine the biological functions and potential pathways of LINC00511 in breast cancer. Then, LINC00511 and key genes associated with breast cancer disease progression were further studied in TCGA (The Cancer Genome Atlas), and western blotting was used to verify the results at the protein level. Finally, we further studied the effect of LINC00511 on Panobinostat drug sensitivity in breast cancer and its effect on the prognosis of breast cancer patients.

Results: LINC00511 was upregulated in breast cancer patients. The expression of LINC00511 was closely related to lymph node metastasis, tumor size and molecular subtypes of breast cancer. The in vitro studies revealed that LINC00511 could promote the migration and invasion in MDA-MB-231 and MCF-7 cells. In terms of mechanism, DNA hypomethylation promoted the expression of LINC00511, furthermore LINC00511 promoted the expression of Wnt10A, E2F2, TGFA, and MET, which participate in the progression of breast cancer. In addition, LINC00511 reduced the sensitivity of breast cancer cells to Panobinostat. Moreover, breast cancer patients with a high expression of LINC00511 had a poor prognosis.

Conclusions: DNA hypomethylation promotes the expression of LINC00511 in breast cancer, and LINC00511 promotes the progression of breast cancer by upregulating Wnt10A, E2F2, TGFA and MET. High expression of LINC00511 is associated with poor prognosis. Our study identified the mechanism of LINC00511 upregulation and provides novel information on the progression of breast cancer.

Keywords: Breast cancer; DNA methylation; LINC00511; prognosis.