Investigating the potential clinical significance of long non-coding RNA 00092 in patients with breast cancer

Jingquan Li; Fanghao Lu; Xin Shao; Bosen You

doi:10.21037/atm-22-1956

Investigating the potential clinical significance of long non-coding RNA 00092 in patients with breast cancer

Ann Transl Med. 2022 May;10(10):602. doi: 10.21037/atm-22-1956.

Authors

Jingquan Li¹, Fanghao Lu², Xin Shao³, Bosen You³

Affiliations

¹ Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China.
² Department of Pathophysiology, Harbin Medical University, Harbin, China.
³ Department of Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.

Abstract

Background: Aberrant promoter methylation and its resultant aberrant gene expression are important epigenetic mechanisms that promote the development of breast cancer (BC). However, the prognostic value of this type of methylation-driven gene in BC is unknown.

Methods: To identify DNA methylation-driven long non-coding RNAs (lncRNAs), a comprehensive analysis of RNA-sequencing and DNA methylation data of 1,200 clinical samples was performed. Differentially expressed lncRNAs (DELs) and survival-related lncRNAs in BC were identified using the R package. The function of the lncRNA was evaluated using Kaplan-Meier and receiver operating characteristic (ROC) curve analyses. The expression of the key lncRNA in tissues and cells was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Biological functions of the key lncRNA were analyzed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. The Connectivity Map (CMap) was used to search for small-molecule targeted drugs for the key lncRNA. The functions of the key lncRNA in BC progression were investigated using cell proliferation and cell cycle assays.

Results: A total of 14 methylation-driven lncRNAs, 526 DELs, and 93 survival-associated lncRNAs were identified. The above data were intersected, and a unique lncRNA, LINC00092, was obtained. LINC00092 was hypermethylated and hypoexpressed in both BC tissues and cell lines. LINC00092 was found to be a diagnostic marker for BC, with its low expression being associated with poor prognosis (P=0.013). LINC00092 overexpression inhibited the proliferation and cell cycle of BC cells in vitro. Nimesulide and sulpiride were screened out as potential targeted therapeutic drugs for LINC00092 in BC, and sulpiride was observed to partially reverse the proliferative effect of (small interfer) si-LINC00092 on BC cells.

Conclusions: LINC00092 is a methylation-driven lncRNA in BC and could be a potential therapeutic target for this disease.

Keywords: Breast cancer (BC); cell cycle; long non-coding RNA 00092 (LINC00092); methylation-driven lncRNA; prognosis.