Long Non-Coding RNA NORAD Inhibits Breast Cancer Cell Proliferation and Metastasis by Regulating miR-155-5p/SOCS1 Axis

Abstract

Purpose Non-coding RNA activated by DNA damage (NORAD) has been reported to be a cancer-related long non-coding RNA (lncRNA) implicated in the progression of several cancers; however, its role in breast cancer (BC) has not yet been clarified. Methods Quantitative real-time polymerase chain reaction was used to examine NORAD, microRNA (miR)-155-5p, and suppressor of cytokine signaling 1 (SOCS1) mRNA expression levels. Western blotting was used to analyze SOCS1 protein expression. The malignancy of BC cells was assessed using the cell counting kit-8 (CCK-8), BrdU, and Transwell assays. Bioinformatics analysis, RNA immunoprecipitation assay, and dual-luciferase reporter gene assays were used to verify the targeted relationship between NORAD and miR-155-5p. Additionally, the regulatory effects of NORAD and miR-155-5p on SOCS1 expression were determined by western blotting. Results NORAD expression was significantly reduced in BC cell lines and tissues, and its low expression was associated with poor tumor tissue differentiation. NORAD overexpression repressed BC cell proliferation, migration, and invasion, whereas its knockdown produced the opposite effects. Additionally, miR-155-5p was found to be a target of NORAD, and the biological functions of miR-155-5p and NORAD were counteractive. MiR-155-5p was confirmed to target SOCS1, and SOCS1 was found to be positively regulated by NORAD. Conclusion NORAD suppresses miR-155-5p to upregulate SOCS1, thereby repressing the proliferation, migration, and invasion of BC cells.

The Role of m6A RNA Methylation-Related lncRNAs in the Prognosis and Tumor Immune Microenvironment of Papillary Thyroid Carcinoma

“…Previous studies have demonstrated that NORAD promoted tumor proliferation and progression in non-small-cell lung cancer (Huang Q. et al, 2020), endometrial cancer (Han T. et al, 2020), and melanoma (Chen et al, 2019). In contrast, NORAD serves as a suppressor gene in neuroblastoma (Yu et al, 2020) and breast cancer (Liu et al, 2021), respectively, which is consistent with our results. Li and Wang (2021) reported GABPB1-AS1 competitively bound to miR-330 and reinforced the ZNF367 expression, thereby facilitating glioma cells progression.…”

Promising Biomarkers in Head and Neck Cancer: The Most Clinically Important miRNAs

“…miR-155 is known to be implicated in the development of several types of cancer, such as non-small cell lung cancer [ 217 ], breast [ 218 ], gliοma [ 219 ], colorectal [ 220 ], and HNSCC [ 221 ]. In addition, miR-155 expression levels are increased and correlated with patient survival in hepatocellular carcinoma [ 222 ].…”

Construction of ceRNA Networks Associated With CD8 T Cells in Breast Cancer

“…There is not much research describing the roles of LINC00943, LINC01146, AC092718.4, and AC005332.4 in breast cancer. NORAD expression was considerably decreased in BC samples, and its deficiency was linked with poor tumor tissue development ( 34 ). XIST expression is significantly reduced in BC samples ( 35 ).…”