Long noncoding RNA ZBED3‐AS1 restrains breast cancer progression by targeting the microRNA‐513a‐5p/KLF6 axis

• Published in: Thoracic cancer 2021-10, Vol.12 (20), p.2719-2731
• Main Authors: Fu, Aiqin, Yu, Ze, Zhang, Enning, Song, Jijie
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Binding sites; Bioinformatics; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Cancer therapies; Cell growth; Cell Line, Tumor; Cell Movement - genetics; Cell Proliferation - genetics; Disease Progression; DNA-Binding Proteins - genetics; Down-Regulation; Female; Gene expression; Gene Expression Regulation, Neoplastic; Humans; KLF6; Kruppel-Like Factor 6 - genetics; long noncoding RNA ZBED3‐AS1; Mastectomy; Medical prognosis; Metastasis; Mice; Mice, Inbred BALB C; MicroRNAs; MicroRNAs - genetics; microRNA‐513a‐5p; Original; RNA, Long Noncoding - genetics; Transcription Factors - genetics; viability
• ISSN: 1759-7706; 1759-7714
• DOI: 10.1111/1759-7714.14111

Breast cancer (BC) is the most commonly occurring malignancy in women. This study aimed to investigate the functions of the long noncoding RNA ZBED3‐AS1 (ZBED3‐AS1) in BC and its molecular mechanisms. qRT‐PCR was conducted to access the expression of ZBED3‐AS1, microRNA‐513a‐5p (miR‐513a‐5p), and Kruppel like factor 6 (KLF6) in BC. Additionally, BC cell viability and proliferative capacity were measured by MTT and 5‐Ethynyl‐20‐deoxyuridine (EdU) assays. A transwell assay was used for evaluating BC cell migration and invasion. The interactions among ZBED3‐AS1, miR‐513a‐5p, and KLF6 in BC were confirmed by dual‐luciferase reporter assay. Furthermore, feedback approaches were performed to determine whether ZBED3‐AS1 influences BC cell behaviors by regulating the miR‐513a‐5p/KLF6 axis. The murine xenograft model was established to assess the effect of ZBED3‐AS1 on tumor growth. The expression of ZBED3‐AS1 and KLF6 was reduced, while miR‐513a‐5p expression was elevated in BC. ZBED3‐AS1 elevation attenuated the malignant behaviors of BC cells, including viability, proliferative capacity, migration, and invasion. Mechanical experiments revealed that ZBED3‐AS1 targeted miR‐513a‐5p, and miR‐513a‐5p targeted KLF6 in BC. Feedback approaches validated that miR‐513a‐5p overexpression or KLF6 depletion reversed the inhibitory effects of ZBED3‐AS1 upregulation on viability, proliferative capacity, migration, and invasion of BC cells. Furthermore, ZBED3‐AS1 elevation attenuated the tumor growth in the murine xenograft model. ZBED3‐AS1 hindered the malignant development of BC cells by regulating the miR‐513a‐5p/KLF6 axis, providing a novel therapeutic target in BC. Diagrammatic sketch of the lncRNA ZBED3‐AS1‐miR‐513‐3p‐KLF6 axis in the breast.