LncRNA ZNF582-AS1 Expression and Methylation in Breast Cancer and Its Biological and Clinical Implications

Abstract

Background: Long non-coding RNAs (lncRNAs) play an important role in cellular activities and functions, but our understanding of their involvement in cancer is limited. Methods: TCGA data on RNA expression and DNA methylation were analyzed for lncRNAs’ association with breast cancer survival, using the Cox proportional hazard regression model. Fresh tumor samples and clinical information from 361 breast cancer patients in our study were used to confirm the TCGA finding on ZNF582-AS1. A RT-qPCR method was developed to measure ZNF582-AS1 expression. Survival associations with ZNF582-AS1 were verified with a meta-analysis. In silico predictions of molecular targets and cellular functions of ZNF582-AS1 were performed based on its molecular signatures and nucleotide sequences. Results: ZNF582-AS1 expression was lower in breast tumors than adjacent normal tissues. Low ZNF582-AS1 was associated with high-grade or ER-negative tumors. Patients with high ZNF582-AS1 had a lower risk of relapse and death. These survival associations were confirmed in a meta-analysis and remained significant after adjustment for tumor grade, disease stage, patient age, and hormone receptor status. Correlation analysis indicated the possible suppression of ZNF582-AS1 expression by promoter methylation. Bioinformatics interrogation of molecular signatures suggested that ZNF582-AS1 could suppress tumor cell proliferation via downregulating the HER2-mediated signaling pathway. Analysis of online data also suggested that HIF-1-related transcription factors could suppress ZNF582-AS1 expression, and the lncRNA might bind to hsa-miR-940, a known oncogenic miRNA in breast cancer. Conclusions: ZNF582-AS1 may play a role in suppressing breast cancer progression. Elucidating the lncRNA’s function and regulation may improve our understanding of the disease.

Long non-coding RNA AC099850.4 correlates with advanced disease state and predicts worse prognosis in triple-negative breast cancer

“…Compelling data have implicated lncRNAs in regulating various biological processes, which could play oncogenic or tumor suppressor roles in breast cancer (12)(13)(14)(15). Our data recently highlighted the prognostic and therapeutic functions of MALAT1 and LINC00511 in TNBC (16,17).…”

Construction of a predictive model for breast cancer metastasis based on lncRNAs

“…This is consistent with the findings of previous research. Notably, Wang et al (31) showed that the expression of ZNF582-AS1 was downregulated in breast cancer tissues. Patients with high expressions of ZNF582-AS1 have a good prognosis and a low recurrence rate.…”

LINC00969 inhibits proliferation with metastasis of breast cancer by regulating phosphorylation of PI3K/AKT and ILP2 expression through HOXD8

“…Recent studies have identified multifarious lncRNAs that are aberrantly expressed in various cancers, including BC, and play a dynamic role in gene regulation ( Reggiardo, Maroli & Kim, 2022 ; Smolarz, Zadrozna-Nowak & Romanowicz, 2021 ). For instance, lncRNA ZNF582-AS1 expression was inhibited in BC tissues and its high expression was also related to a lower risk of relapse and death ( Wang et al, 2022 ). LncRNA SNHG14 was remarkably elevated and silencing SNHG14 remarkably mitigates BC cell proliferation, migration, invasion, and facilitates apoptosis ( Zhang, Ding & Peng, 2022 ).…”